We prospectively studied patients with Streptococcus bovis septicemia for the presence of gastrointestinal lesions. This study was prompted by our reported findings of the association of fecal carriage of S. bovis with carcinoma of the colon. We studied 29 patients with 30 episodes of S. bovis septicemia. Fifteen completed gastrointestinal evaluations that included colonscopy, surgery, or autopsy. Eight of these had carcinoma of the colon, three had adenomatous polyps of the colon without carcinoma, and two had carcinoma of the esophagus. The 14 patients who did not have complete evaluations included one each with carcinoma of the stomach, gastric lymphoma, and adenomatous polyp of the colon and three with colonic masses not further delineated. Nineteen patients had no gastrointestinal signs or symptoms or stools positive for occult blood at admission. The results of our study suggest that all patients with S. bovis septicemia need aggressive evaluation of the gastrointestinal tract, especially the colon.