In patients with previous myocardial infarction (MI), depressed heart rate variability (HRV) may reflect a reduction in vagal activity and lead to cardiac electrical instability. Interventions designed to increase HRV may be of clinical interest. Data on the effects of calcium antagonists on HRV in post-MI patients are very limited. The aim of our study was to assess the effects of verapamil on HRV and on the sympathovagal balance after MI. Fifty consecutive patients with a first MI, stable sinus rhythm, and left ventricular ejection fraction >0.40 were studied. Each patient underwent two 24-hour Holter recordings, 1 at baseline and another after 4 days of treatment with verapamil retard (180 mg 2 times daily). Time and frequency domain parameters of HRV were analyzed. All time domain measurements increased significantly after verapamil: the standard deviation of all NN intervals (SDNN) from 87.1 +/- 31.4 to 98.1 +/- 30.3 ms (p <0.05) and the log-transformed percentage of pairs of adjacent NN intervals that differ >50 ms (pNN50) from 0.57 +/- 0.42 to 0.76 +/- 0.45 (p <0.01). The standard deviation of the averages of RR interevals (SDANN) (75.9 +/- 30.1 vs 86.3 +/- 29.4 ms, p <0.05), root-mean-square of successive differences between RR intervals (rMSSD) (23.0 +/- 11.7 and 28.1 +/- 13.1 ms, p <0.01), and the triangular HRV index (28.3 +/- 9.6 vs 23.4 +/- 8.6, p <0.001) also increased. A significant inverse correlation was found between improvement in HRV indexes induced by verapamil and baseline values. Spectral analysis showed a significant increase in high-frequency power of 58.5% without changes in low and very low components. With normalized units, significant reductions in low-frequency power and low- to high-frequency ratio were observed. Diabetic patients did not show any significant changes in HRV on administration of verapamil. These findings indicate that verapamil, administered during the subacute phase of MI, improves both global and short-period indexes of HRV and induces a shift in the sympathetic-parasympathetic interaction toward vagal predominance. This effect may contribute to an explanation of the beneficial effects of verapamil that have been reported in post-MI patients.