We define the clinical importance of cytomegalovirus (CMV) in the natural history of patients with concomitant candida and CMV infection of the esophagus. Prospective evaluation was made of patients with Candida and CMV esophagitis enrolled in a trial of antifungal therapy for Candida esophagitis. Retrospective review was also made of the course of patients who had been found to have both Candida and CMV infection during a previous prospective endoscopic study investigating the etiology of esophageal symptoms in HIV infection. Ten (21%) of 48 patients with Candida esophagitis in the prospective study had evidence of esophageal CMV (nine by culture, one by histology). One died after 4 weeks of therapy, with minimal retrosternal pain. None of the remaining nine had any symptoms or gross CMV esophagitis after antifungal therapy. Thirteen other patients with CMV and Candida were included in the retrospective review (mean follow-up of 8 months). Eight patients received antifungal therapy alone: six (CMV determined by histology in three and by culture in three) had symptomatic resolution; one (CMV by culture) had ongoing symptoms, and a second endoscopy showed an esophageal ulcer due to CMV (histology and culture); and one had ongoing symptoms but a negative repeat endoscopy. Two died without receiving treatment, and three were treated with antifungal and anti-CMV therapy together because of concurrent CMV retinitis (esophageal symptoms resolved in all three). Thus, CMV was of clinical importance in the esophagus in only one of 18 patients with CMV and Candida who received antifungal therapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)