The influence of perioperative blood transfusion on postoperative depression of cell-mediated immunity (CMI) and the effect of ranitidine on transfusion-induced changes in postoperative CMI were investigated. CMI was assessed preoperatively and postoperatively by skin testing with seven common delayed-type antigens in 83 consecutive patients undergoing major elective abdominal surgery. Sixty-six of these patients were randomly divided into ranitidine or no-ranitidine-treatment groups, and the remaining 17 patients were operated on without ranitidine. Thus, 50 patients were operated on without ranitidine therapy, and whole blood transfusion was given to 24 of these patients. Postoperative skin test response was more reduced in transfused vs nontransfused patients (-57% vs -38%, p less than 0.0001). Fourteen of the 24 patients receiving blood transfusion could be exactly matched to 14 patients not receiving transfusion (age, sex, B-hemoglobin, S-albumin, type and duration of surgery, etc.), which confirmed that a more pronounced reduction in postoperative skin test response was found in transfused patients (-55% vs -31%, p less than 0.0001). Seventeen of the 33 patients treated with perioperative ranitidine, 50 mg intravenously every 6 hours for 72 hours, received perioperative blood transfusion. Eleven of these patients could be matched to 11 transfused patients not receiving perioperative ranitidine. Ranitidine prevented postoperative reduction in skin test response (+6% vs -55%, p less than 0.0001). It is concluded that perioperative transfusion with whole blood amplifies the postoperative impairment in delayed hypersensitivity and that transfusion-induced postoperative impairment in delayed hypersensitivity may be prevented by perioperative ranitidine treatment.