The effects of oral diltiazem (90-180 mg/day for four weeks) on ventricular premature contractions (VPCs) were studied in 16 patients with frequent VPCs using 24-hour ambulatory ECG recordings. VPC frequency was evaluated as a function of underlying heart rate. Plots of VPC frequency vs. heart rate were made at 1-beat/min intervals for all heart rates recorded for at least five minutes during 24 hours. Patterns of correlation between VPC frequency and heart rate observed before diltiazem therapy included: 1) a relatively linear increase in VPCs with heart rate (positive correlation) in ten patients, 2) a linear decrease (negative correlation) in one patient, and 3) an increase at low heart rates and a decrease at high heart rates (bidirectional correlation) in five patients. Diltiazem significantly reduced the mean VPC frequency per 24 hours for patients with a positive correlation, but induced no significant change for patients with a negative or a bidirectional correlation. At the 65% level of VPC reduction, diltiazem was effective in eight of ten patients with a positive correlation but was not effective in the six patients with other correlations (p less than 0.01). These results suggest that an evaluation of VPC frequency as a function of heart rate predicts the response of VPCs to diltiazem.