Diltiazem was administered to dogs by intravenous infusion to achieve plasma levels of 47 +/- 3 (n = 7), 148 +/- 12 (n = 8), 263 +/- 10 (n = 8), and 379 +/- 43 (n = 8) ng X ml-1, to evaluate the effects of diltiazem on cardiovascular function and coronary hemodynamics, when given in the presence of anesthetic concentrations of isoflurane. Plasma level related prolongation of the PR interval of the electrocardiogram was the most prominent effect observed, with development of 2 degrees heart block or junctional rhythms in several of the animals at the two higher plasma levels. Mean arterial pressure, transiently decreased after the loading dose in all groups, was no different from control values after 30 min of infusion. Left ventricular dP/dt was mildly decreased at the three highest plasma levels, whereas right and left heart filling pressures were increased at the two highest plasma levels. Cardiac index and systemic vascular resistance were unchanged. No changes were observed in coronary sinus blood flow, coronary vascular resistance, myocardial oxygen uptake, myocardial lactate extraction, or circulating epinephrine or norepinephrine levels in any of the groups. In the presence of anesthetic concentrations of isoflurane, over the range of plasma levels investigated in this study, the vasodilating properties of diltiazem were not observed, yet conduction effects were prominent and decreases in left ventricular performance occurred. No untoward effects on global myocardial metabolism were detected under these conditions.