The effect of perioperative immunomodulation with the H2-receptor antagonist ranitidine on postoperative changes in soluble interleukin (IL) 2 receptor and soluble CD8 levels was assessed in 24 patients undergoing major elective abdominal surgery. Eleven patients were randomized to receive intravenous ranitidine 100 mg twice daily for 4 days from skin incision, followed by oral ranitidine 150 mg twice daily for a further 5 days; 13 control patients received no ranitidine. Routine blood analysis, clinical data, duration of surgery, anaesthesia, antibiotic prophylaxis and perioperative blood transfusion were similar in the two groups. Serum concentrations of soluble IL-2 receptor and CD8 were measured before operation (day 0) and in the morning of postoperative days 1, 3 and 9 using commercial enzyme-linked immunosorbent assay kits. In patients treated with ranitidine, the serum level of soluble IL-2 receptor increased from day 0 to day 9 (P < 0.01); in control patients it decreased from day 0 to day 1, did not change significantly by day 3 and increased by day 9. The change from day 0 to day 1 was significantly different between the two groups (P < 0.01). Five of the 13 control patients developed postoperative infectious complications. No significant differences were shown in soluble CD8 concentration during the postoperative period. The postoperative change in soluble IL-2 receptor level may reflect lymphocyte activation status; ranitidine appears to promote activation of mainly CD4-positive lymphocytes since serum levels of CD8 were unchanged. Ranitidine may, therefore, improve immune function during major surgery.