In order to study the pharmacokinetics of famotidine in cardiac surgery patients, we administered famotidine 20mg by intravenous injection at the beginning of surgery and 12 hours after surgery in 8 patients undergoing elective cardiac surgery with cardiopulmonary bypass. Total body clearance, volume of distribution, and elimination half-life were calculated using noncompartmental analysis and compared with published normal parameters (control) using a 2-tailed, 1 -sample t-test. Intra- and postoperative clearances were 2.93 ± 1.06 and 3.18 ± 1.06 ml/min/kg, respectively, which were more than 50% less than the control value (6.07 ml/min/kg; p<0.0005). The volume of distribution (1.0 L/kg) was unaltered during the study and did not differ from the control value (1.19 L/kg; p>0.08). Intra- and postoperative half-lives were 4.52 ± 2.21 hours and 4.27 ± 1.58 hours, respectively, which were more than 50% longer than control (2.92 hours; p<0.03). Famotidine pharmacokinetics are significantly altered during cardiac surgery with cardiopulmonary bypass, and these changes persist for up to 24 hours after surgery.