A depressed heart rate variability (HRV) is a powerful predictor of poor outcome in myocardial infarction patients. The beneficial effect of specific interventions on its recovery has been reported, but data concerning calcium antagonists are scarce. We evaluated the effect of a phenylalkylamine derivative, verapamil, and a dihydropyridine derivative, felodipine, on time- and frequency-domain measurements of HRV by 24-hour Holter monitoring in 60 patients with acute myocardial infarction (AMI). After a first Holter recording (65 +/- 8 hours from the onset of symptoms), patients were randomly assigned to continue standard treatment or to also receive verapamil retard (120 mg 3 times daily) or felodipine extended-release (10 mg/day). Holter recording was repeated after 7 days. After verapamil, mean RR interval increased from 823 +/- 92 to 907 +/- 95 ms and the SD of all normal RR (NN) intervals (SDNN) from 99 +/- 24 to 120 +/- 30 ms (p < 0.01); the root mean square successive difference (r-MSSD) and the percent of differences between adjacent NN intervals > 50 ms (pNN50) also increased (p < 0.01). After felodipine, only SDNN increased (p < 0.01). Regarding frequency-domain measurements, after receiving verapamil, very low frequency, low- and high-frequency powers increased (p < 0.01), whereas the low- to high-frequency ratio decreased (p < 0.01). After receiving felodipine, very low-frequency power increased (p < 0.01), whereas low- and high-frequency powers and the low- to high-frequency ratio remained unchanged. This study demonstrates that verapamil, but not felodipine, improves HRV in the early phase after AMI.