The efficacy of prophylactic administration of H1 and H2 receptor blockers to prevent adverse haemodynamic responses to heparin and protamine was studied. The control group (n = 10) received no histamine receptor blocker; group HI (n = 10) received oral terfenadine 60 mg, group H2 (n = 10) received oral ranitidine 300 mg, and group H1 + H2 (n 10) received both terfenadine and ranitidine on the night before the operation and on call to the operating room. Heparin sulphate 300 U/kg was injected directly into the right atrium, and protamine hydrochloride was administered at the conclusion of bypass over at least three minutes through a peripheral route. Following the injection of heparin, plasma histamine-like activity (H-LA) was increased significantly in all four groups. While systolic, diastolic, mean arterial and central venous pressures were decreased significantly in the control group, no significant changes were observed in the HI and H2 groups. Protamine infusion did not lead to an increase in H-LA. Prophylactic administration of histamine receptor blockers (H1 or H2) attenuated the heparin-induced adverse haemodynamic response but did not change the protamine-related haemodynamic effects. Factors other than histamine may play a major role in protamine induced cardiovascular changes.