diff --git a/.github/workflows/e2e-nightly.yml b/.github/workflows/e2e-nightly.yml
new file mode 100644
index 000000000..96b406961
--- /dev/null
+++ b/.github/workflows/e2e-nightly.yml
@@ -0,0 +1,43 @@
+# Runs randomly generated E2E testnets nightly.
+name: e2e-nightly
+on:
+  workflow_dispatch: # allow running workflow manually
+  schedule:
+    - cron: '0 2 * * *'
+
+jobs:
+  e2e-nightly-test:
+    # Run parallel jobs for the listed testnet groups (must match the
+    # ./build/generator -g flag)
+    strategy:
+      fail-fast: false
+      matrix:
+        group: ['00', '01', '02', '03']
+    runs-on: ubuntu-latest
+    timeout-minutes: 60
+    steps:
+      - uses: actions/checkout@v2
+
+      - name: Build
+        working-directory: test/e2e
+        # Run make jobs in parallel, since we can't run steps in parallel.
+        run: make -j2 docker generator runner
+
+      - name: Generate testnets
+        working-directory: test/e2e
+        run: ./build/generator -g 4 -d networks/nightly
+
+      - name: Run testnets in group ${{ matrix.group }}
+        working-directory: test/e2e
+        run: sudo ./run-multiple.sh networks/nightly/*-group${{ matrix.group }}-*.toml
+
+      - name: Notify Slack on failure
+        uses: rtCamp/action-slack-notify@e9db0ef
+        if: ${{ failure() }}
+        env:
+          SLACK_WEBHOOK: ${{ secrets.SLACK_WEBHOOK }}
+          SLACK_CHANNEL: tendermint-internal
+          SLACK_USERNAME: Nightly E2E Test Failure
+          SLACK_COLOR: danger
+          SLACK_MESSAGE: Nightly E2E test failed (group ${{ matrix.group }})
+          SLACK_FOOTER: ''
diff --git a/test/e2e/networks/ci.toml b/test/e2e/networks/ci.toml
index e366bb6c5..12478ef99 100644
--- a/test/e2e/networks/ci.toml
+++ b/test/e2e/networks/ci.toml
@@ -26,11 +26,11 @@ validator05 = 50
 
 [node.seed01]
 mode = "seed"
-persistent_peers = ["seed02"]
+seeds = ["seed02"]
 
 [node.seed02]
 mode = "seed"
-persistent_peers = ["seed01"]
+seeds = ["seed01"]
 
 [node.validator01]
 seeds = ["seed01"]
diff --git a/test/e2e/runner/load.go b/test/e2e/runner/load.go
index a59b3f503..495c573d3 100644
--- a/test/e2e/runner/load.go
+++ b/test/e2e/runner/load.go
@@ -16,9 +16,17 @@ import (
 // Load generates transactions against the network until the given
 // context is cancelled.
 func Load(ctx context.Context, testnet *e2e.Testnet) error {
-	concurrency := 50
+	// Since transactions are executed across all nodes in the network, we need
+	// to reduce transaction load for larger networks to avoid using too much
+	// CPU. This gives high-throughput small networks and low-throughput large ones.
+	// This also limits the number of TCP connections, since each worker has
+	// a connection to all nodes.
+	concurrency := 64 / len(testnet.Nodes)
+	if concurrency == 0 {
+		concurrency = 1
+	}
 	initialTimeout := 1 * time.Minute
-	stallTimeout := 15 * time.Second
+	stallTimeout := 30 * time.Second
 
 	chTx := make(chan types.Tx)
 	chSuccess := make(chan types.Tx)
@@ -26,7 +34,7 @@ func Load(ctx context.Context, testnet *e2e.Testnet) error {
 	defer cancel()
 
 	// Spawn job generator and processors.
-	logger.Info("Starting transaction load...")
+	logger.Info(fmt.Sprintf("Starting transaction load (%v workers)...", concurrency))
 	started := time.Now()
 
 	go loadGenerate(ctx, chTx)
diff --git a/test/e2e/runner/start.go b/test/e2e/runner/start.go
index bf52e190e..915222faf 100644
--- a/test/e2e/runner/start.go
+++ b/test/e2e/runner/start.go
@@ -24,7 +24,7 @@ func Start(testnet *e2e.Testnet) error {
 		if err := execCompose(testnet.Dir, "up", "-d", node.Name); err != nil {
 			return err
 		}
-		if _, err := waitForNode(node, 0, 10*time.Second); err != nil {
+		if _, err := waitForNode(node, 0, 15*time.Second); err != nil {
 			return err
 		}
 		logger.Info(fmt.Sprintf("Node %v up on http://127.0.0.1:%v", node.Name, node.ProxyPort))
@@ -56,7 +56,7 @@ func Start(testnet *e2e.Testnet) error {
 		if err := execCompose(testnet.Dir, "up", "-d", node.Name); err != nil {
 			return err
 		}
-		status, err := waitForNode(node, node.StartAt, 30*time.Second)
+		status, err := waitForNode(node, node.StartAt, 1*time.Minute)
 		if err != nil {
 			return err
 		}