We studied the comparative vascular effects of midazolam and lorazepam in 52 patients undergoing elective cardiac surgery procedures. After administration of fentanyl, 100 mu g/kg intravenously, the patients were randomized to receive either midazolam 0.1 mg/kg (M high), midazolam 0.05 mg/kg (M low), lorazepam 0.1 mg/kg (L high),lorazepam 0.05 mg/kg (L low), or placebo during cardiopulmonary bypass (CPB). Compared to the placebo and L-low groups, the high-dose midazolam group had more effect on systemic Vascular resistance (SVR) starting at 5 min after study drug administration (p < 0.02). M high and L high required increased quantities of phenylephrine administered to maintain the mean arterial pressure (MAP) at >50 mm Hg after rewarming and removal of the aortic crossclamp (P < 0.03). In the first 12 h of the postoperative period, the M-high group required phenylephrine (PHE) infusion for hypotension associated with decreased SVR more often than placebo (8/10 vs 1/11 patients, P < 0.008, chi(2)). In conclusion, midazolam more effectively attenuated the increase in SVR that occurred during CPB than patients receiving either placebo or lorazepam. The hemodynamic effects from a single dose of 0.1 mg/kg midazolam administered at the start of CPB may persist into the postoperative period.