Ganciclovir (DHPG) treatment of 69 AIDS patients with gastrointestinal infection due to cytomegalovirus (CMV) was studied. Sites of infection included the colon (46 patients, 67%), esophagus and stomach (15 patients, 22%), rectum (five patients, 7%), liver (two patients, 3%), and small bowel (one patient, 1.4%). Ganciclovir was given in a dose of 5 mg/kg intravenously every 12 hours for 14 days. Maintenance therapy consisted of 6 mg/kg daily. Positive clinical responses were seen in 52 (75%) of the 69 patients, stable responses in 9 (13%), and worsening in eight (11%). The virologic response was positive in 47 patients (68%), while virologic findings did not change in three patients (4%) and could not be evaluated in 19 patients (28%). Toxicity was mainly hematologic, with moderate leukopenia (1,000-1,900 leukocytes/mm3) in seven patients and severe leukopenia (less than 1,000 leukocytes/mm3) in three patients. The median survival time was 18 weeks (range, 1-68 weeks). Forty-seven patients survived for 4 weeks; of these, 22 (47%) relapsed. The median time to relapse was 9 weeks. Despite the uncontrolled nature of this study, ganciclovir is probably an effective and safe agent for the treatment of gastrointestinal CMV infections. The high probability of relapse (50%) should be considered and maintenance therapy offered to most patients.