The effects of two selective histamine H2 receptor antagonists on delayed-type hypersensitivity to sheep red blood cells were studied in Balb/c mice. While cimetidine significantly enhanced DTH response when given from immunization to challenge via the intraperitoneal route (10-30 mg/kg twice daily), ranitidine (5-20 mg/kg) did not produce any effect. Both drugs proved ineffective on acquisition as well as expression of DTH. These results suggest that most immunopharmacological effects of cimetidine may not be mediated through histamine H2 receptors, but may possibly be mediated through its imidazole moeity.