Major surgical trauma has been considered as a cause of immunosuppression mainly through the production of prostaglandin E2 from activated monocytes/macrophages. In the present study we investigated the effect of parenteral indomethacin--a cyclo-oxygenase inhibitor--on T-lymphocyte subsets and cytokine production in patients under major operations. We studied 20 patients undergoing major surgical procedures, 10 of whom were randomly treated pre- and post-operatively with indomethacin (group 2) and 10 were not (group 2). We measured total T-cells, T-helper, T-suppressor, T-helper/T-suppressor (Th/Ts) cell ratio, NK-cells and interleukin (IL-1) and tumor necrosis factor production by endotoxin- or phytohemagglutinin-stimulated peripheral blood mononuclear cells, before operation and at days 1, 3 and 7 postoperatively. We detected a significant increase in Th/Ts cell ratio and an improvement in delayed type hypersensitivity response in the treated group at day 3. We believe that the above immunomodulating effect of in vivo cyclo-oxygenase inhibition may be beneficial in patients under major surgical procedures with a high susceptibility to postoperative infections.