The effect of cimetidine treatment on the generation of interleukin-1 (IL-1) and interleukin-2 (IL-2) was studied in 11 duodenal ulcer patients. The results obtained were compared with those for untreated healthy subjects. The drug was administered intravenously in a dose of 200 mg four times a day for 8 days. The investigations were performed before, during and 1 wk after cimetidine therapy. IL-1 generation was determined by the ability of supernatants from 2-day cultured adherent cells stimulated by lipopolysaccharide to enhance proliferation of PHA-stimulated mice thymocytes. IL-2 generation was determined by the ability of supernatants from 2-day cultured, PHA-stimulated mononuclear cells to proliferate autologous 17-day cultured T cells. In all ulcer patients IL-1 generation diminished during cimetidine treatment (P less than 0.005). It continued to decrease in 4 subjects and increased in the other 7 ones following drug withdrawal. All the values were higher than those in healthy controls. IL-2 activity in ulcer patients was similar to that in healthy subjects and it increased significantly in all ulcer patients following the onset of the treatment (P less than 0.005) and decreased nearly to the initial values 1 wk after termination of the treatment (P less than 0.005). The present studies indicate that cimetidine, a selective histamine H2-receptor antagonist, deeply changes mechanisms of immunoregulation in patients with duodenal peptic ulcer.