Administration of carrageenan to guinea pigs produces colonic lesions which are similar to those noted in idiopathic ulcerative colitis of human beings. This model was used to determine fecal flora changes and response to antimicrobial probes during the evolution of carrageenan-induced colitis. The results of fecal flora analysis showed that mean coliform concentrations increased from 10(2.7) to 10(7.4) per g during the initial stages of colonic ulceration. Pretreatment of carrageenan recipients with antimicrobials directed against coliforms reduced the concentrations of these organisms, but failed to attenuate the disease process. On the other hand, pretreatment with metronidazole, an antimicrobial primarily active against anaerobic bacteria, prevented carrageenan-induced colitis in a majority of animals. Delayed treatment with metronidazole until after colitis was established showed no salutory benefits. These results suggest that anaerobic bacteria play a role in the initial events of carrageenan-induced colitis in the guinea pig model.