The hemodynamic response to nafcillin administration was studied in 45 patients with good left ventricular function and no known history of hypersensitivity to penicillin during coronary artery bypass grafting (CABG). Group I (15 patients) received 1 gram of nafcillin in 10 mL of saline as an intravenous (IV) bolus, group II (15 patients) received 1 gram of nafcillin in 50 mL of saline as a slow IV infusion over 15 minutes, and group III (15 patients) did not receive nafcillin. Hemodynamic variables and plasma histamine and catecholamine levels were measured before and after nafcillin administration, after 500 mg of CaCl2, and after 0.1 mg of phenylephrine. Bolus nafcillin administration produced profound hypotension secondary to vasodilatation with significant increases in cardiac index and decreases in systemic and pulmonary vascular resistances. Cardiac index increased from 3.15 +/- 0.3 L/min/m2 to 5.75 +/- 0.25 L/min/m2 (P less than 0.005) one minute after nafcillin administration, and remained at 5.1 +/- 0.35 L/min/m2 after administration of CaCl2 (P less than 0.005). All hemodynamic parameters returned toward control values after administration of 0.1 mg of phenylephrine, IV. Plasma epinephrine, norepinephrine, and histamine levels increased more than 100%. In group II, cardiac index increased, while systemic and pulmonary vascular resistances and mean arterial pressure decreased. However, these changes were less significant than those found in group I.(ABSTRACT TRUNCATED AT 250 WORDS)