It is difficult to understand how a disease process characterized by ulcerations, fissures, abscesses, fistulas, lymphangitis, and granulomas has not attracted greater use of antibiotics, particularly as the sites are constantly contaminated by intestinal bacteria. I have had a favorable experience with broad-spectrum antibiotics in the treatment of a variety of forms of ileocolitis in animals and now advocate that Crohn's disease be treated at length with these drugs. Microbiologic culture of serosa, mesenteric lymph nodes, and fistulas has demonstrated that bacterial species are present in a significant proportion of cases, and serology has shown that patients have elevated antibody levels to many of these same microorganisms. Now immunocytochemistry provides documentation of Escherichia coli and streptococcal antigen within the lesions of a majority of patients. That these bacteria may be secondary invaders should not decrease our need to address them. Several chronic granulomatous diseases that were once thought to be intractable now yield to long-term antibiotic treatment, including Whipple's disease, malakoplakia, and granulomatous colitis of Boxer dogs. Many of the perianal lesions of Crohn's disease respond to short-term metronidazole, and the medium-term (3-6 months) use of broad-spectrum antibiotics, most recently ciprofloxacin, has shown promising results. In view of the increasing evidence of bacterial participation in this disease, it is now important that physicians test some of our newer broad-spectrum antibiotics, in a controlled format, and over an extended time.