In a group of 29 AIDS patients with biopsy-proven human cytomegalovirus (HCMV) gastrointestinal disease (GID), HCMV GID was shown to correlate mostly with systemic HCMV infection. The antiviral induction treatment (IT) with either ganciclovir (GCV) or foscarnet (PFA) caused a significant reduction in the level of HCMV antigenemia, viremia and leukoDNAemia, and a complete virus clearance or a sharp drop of viral load in the blood of 13/13 patients and in the gastrointestinal (GI) mucosa of 12/13 (92%) patients in the GCV arm, and in the blood of 13/14 (93%) patients and in the GI mucosa of 10/12 (83%) patients in the PFA arm of the study, respectively. Similarly, the clinical response was good in 13/15 (87%) patients in the GCV arm and in 13/14 (93%) patients in the PFA arm. In addition, the finding that 2/6 patients positive for HCMV isolated from both GI mucosa and blood prior to IT were still positive in the GI tract after IT, suggested that IT could be prolonged to clear the virus from GI tract. In conclusion, both GCV and PFA showed a remarkable systemic and local antiviral effect in the treatment of HCMV GID in AIDS patients.