A study has been undertaken of the granulomatous response induced in the ascending colon and terminal ileum of the guinea pig by the direct inoculation of mycobacterial antigens. Live BCG (Pasteur) 2 x 10(7) at two weeks induced epithelioid cell granulomas in both large and small bowel and in the draining lymph nodes. The area of infiltration was significantly greater for a given inoculum in the large bowel. Acid fast bacilli were present on Ziehl Neelson stained sections of the large bowel infiltrate, but only rarely in sections from the small bowel lesions. The response to skin testing with a standardised amount of purified protein derivative was less in animals inoculated in the small bowel. Inoculation with 2 x 10(9) cobalt irradiated BCG gave rise, at five weeks, to granulomas containing lesser numbers of epithelioid cells and caseation was sometimes evident. There was a similar but smaller difference in the degree of infiltration at the two inoculation sites. Ziehl Neelson staining failed to reveal the presence of acid fast bacilli in any sections of the bowel infiltrates. Skin testing with purified protein derivative gave a response which was greater in animals inoculated in the small bowel. An identical dose of Cobalt irradiated M leprae induced at five weeks a predominantly macrophage granuloma in both the large and small bowel, with no significant difference in the degree of infiltration at the two sites. No acid fast bacilli were seen in Ziehl Neelson stained sections of the bowel and skin testing with purified protein derivative was reduced. These findings and their relevance to studies of the aetiology of Crohn's disease are discussed.