Forty hemodynamically stable patients were randomized to receive an intravenous bolus of either calcium chloride (5 mg/kg) (n = 20) or placebo (n = 20) (phase I). Six minutes later, they received either an epinephrine (30 ng·kg-1·min-1) (n = 20) or placebo (n = 20) infusion (phase II). Hemodynamic and ionized calcium measurements were obtained in phase I at baseline and at 3 and 6 min after the bolus, and in phase II, at 3 and 6 min (study times 9 and 12 min) after initiation of the infusion. Compared with placebo, calcium did not significantly increase cardiac index but significantly increased mean arterial pressure. Calcium improved cardiac index from 2.46 ± 0.12 (mean ± SEM) to 2.74 ± 0.12 L·min-1·m-2; likewise, placebo improved cardiac index from 2.51 ± 0.15 to 2.74 ± 0.15 L·min-1·m-2. Mean arterial blood pressure increased with calcium from 74 ± 2 to 82 ± 3 mm Hg compared with a placebo change of 74 ± 2 to 76 ± 2 mm Hg. Patients who received the epinephrine infusion (n = 20) demonstrated a significant increase in cardiac index at time 12 min compared with patients receiving only placebo (n = 20). Cardiac index of the epinephrine group increased from 2.56 ± 0.15 to 2.92 ± 0.22 L·min-1·m-2, whereas in the placebo group it decreased from 2.86 ± 0.13 to 2.78 ± 0.12 L·min-1·m-2. Prior administration of calcium did not alter the subsequent response to epinephrine (n = 10) compared with patients receiving epinephrine alone (n = 10). We conclude that cardiac index improves with time without drug therapy after bypass. Calcium chloride increases mean arterial blood pressure but not cardiac index immediately after cardiopulmonary bypass, whereas low-dose epinephrine significantly increases both cardiac index and mean arterial blood pressure without causing tachycardia in these patients. Calcium chloride (5 mg/kg) did not augment or inhibit the hemodynamic response to an epinephrine infusion.