Patients with symptomatic gastrointestinal disease due to cytomegalovirus (CMV) were randomized to receive open-label ganciclovir (22) or foscarnet (26). Patients were stratified by disease site and concurrent gut infection. Response was assessed by a visual analogue score of symptoms, endoscopic appearances, histologic inflammation, and numbers of CMV inclusions. In each treatment group, 73% had a complete or good clinical response; 83% of foscarnet-treated and 85% of ganciclovir-treated patients showed response by endoscopy, and inclusion bodies disappeared from follow-up biopsies in 73% of these. Most patients (35) developed further evidence of CMV disease during follow-up. The time to progression was not significantly different between recipients (16 weeks) and nonrecipients (13 weeks) of maintenance therapy, although patients were not randomized to receive maintenance or not. Survival in both treatment groups was < 40 weeks and was unaffected by maintenance treatment. Both ganciclovir and foscarnet are effective first-line treatments for gastrointestinal (GI) CMV infection. Maintenance therapy does not prevent progression of disease.