Fifty patients with idiopathic ulcerative colitis-25 with acute exacerbation of the disease (Group I) and 25 in quiescent phase (Group II)-were studied. None of the patients had a history of recent exposure to antimicrobial drugs or hospitalization. Evidence of infection with protozoal and bacterial agents and/or presence ofClostridium difficiletoxin was demonstrated in eight (32%) patients in group I and one (4%) patient in group II (group I vs. group II, p < 0.05; X2test with Yate's correction). In five of the six patients with demonstrableClostridium difficiletoxin in the stool, one patient with Entamoeba trophozoites, and another with Salmonella infection, the exacerbation responded clinically and endoscopically to specific antimicrobial therapy. Another two patients who hadEntamoeba histolyticacysts in the stool had no change in their clinical status with metronidazole. We conclude that infectious agents are responsible for some of the exacerbations in patients of ulcerative colitis in a tropical country like India, where careful microbiologic examination is in order in every acute exacerbation of this disease. This contrasts with the findings in developed countries.