Surgical procedures probably result in a temporary state of immunosuppression. Identification of functional lymphocyte subclasses using appropriate monoclonal antibodies appears to serve as a sensitive, accurate, and reproducible measure of immune status in patients in many disease states. Using monoclonal antibodies specific for lymphocyte surface markers and immunofluorescent assay, we quantitated lymphocyte subpopulations in patients undergoing surgical procedures. Cholecystectomy, colon surgery, and coronary bypass procedures all resulted in postoperative decreases in helper and inducer populations and increases in cytotoxic suppressor populations, with resultant depressions in the helper to suppressor lymphocyte ratio. Studies in an additional group of patients who underwent cholecystectomy demonstrated that these changes could be prevented by perioperative administration of ibuprofen and cimetidine. These results suggest that prostaglandins and histamines are involved in immunoregulatory events after major operation. The ability of specific pharmacologic therapy to prevent alterations in lymphocyte populations suggest that postoperative immunity may be preserved, hopefully leading to greater host resistance against infection and tumor dissemination.