To determine the hemodynamic effect of different programmed atrioventricular (AV) delays and the importance of the actual timing of left atrial (LA) depolarization, 16 patients with dual-chamber pacemakers were studied and all were found to have an optimal programmed AV delay for cardiac function. However, randomly chosen AV delays of 150, 200 or 250 ms actually provided worse stroke volume than VVI pacing in 7 patients. The optimal programmed AV delay was variable between patients and was related to the interatrial conduction delay, measured as the time from right atrial pacing artifact to LA depolarization (mean 144 +/- 82 ms, range 70 to 380.) Patients with short interatrial delays (less than or equal to 90 ms) were served better by shorter programmed AV delays (150 ms), and patients with longer interatrial delays (greater than or equal to 120 ms) were served better by longer programmed AV delays (greater than or equal to 200 ms) (p less than 0.05). Furthermore, as pacing mode changed from dual-chamber sequential pacing (DVI) to atrial synchronous ventricular pacing (VDD), the LA to ventricular sequence increased from 6 +/- 81 ms to 137 +/- 50 ms (p less than 0.001). This change in the LA to ventricular sequence with mode change produced a significant decrease in stroke volume (p less than 0.05). Thus, the optimal programmed AV delay in patients with dual-chamber pacemakers is predicted by the relation of LA and ventricular activation. Because interatrial conduction delays vary widely, optimal programming requires knowledge of the LA to ventricular sequence.(ABSTRACT TRUNCATED AT 250 WORDS)