Cytomegalovirus (CMV) is a major cause of inflammatory organ disease in immunosuppressed persons. To elucidate the mechanisms of CMV-induced inflammation, we investigated whether tumor necrosis factor-a (TNF-a) was involved in the pathogenesis of CMV colitis in patients with AIDS. In in situ hybridization experiments, TNF-a mRNA was shown to be abundantly present in colonic mucosa from AIDS patients with CMV colitis but not in colonic mucosa from control (AIDS and normal) subjects. The TNF-a transcripts, identified in macrophage-like cells containing cytomegalic inclusions, were positively associated with CMV, but not HIV-1, within the mucosa.