It was hypothesised that different immune responses would be obtained following oral and colonic antigen administration, due to the significant differences in the immune environments of the colon and that of the small intestine. Antigen administration to the mouse colon (via the rectum) was found to generate different profiles of immune responses compared to oral administration (by gavage). Serum IgG and IgA levels in faecal and colonic extracts and in the vaginal wash were significantly higher following colonic administration of soluble (plus cholera toxin B subunit adjuvant) or encapsulated (in microspheres) antigen while smaller differences were seen in the small intestinal IgA levels. This reflects the compartmentalisation within the common mucosal immune system and suggests that the colon may be an appropriate vaccination target for diseases of the colon, and for sexually and vertically transmitted diseases. Antigen was also administered rectally and intramuscularly as controls. Colonic administration was superior to rectal administration, possibly due to the greater amounts of lymphoid tissue in the colon, although the immune response profiles were similar.