CMV infection of the central nervous system in immunocompromised adults, such as AIDS patients, can cause devastating neuropathology. Since cytokines play a pivotal role in inflammatory responses and may be important mediators of central nervous system dysfunction, we investigated the role of transforming growth factor (TGF-Beta) in the pathogenesis of CMV encephalopathy. Brain tissue from AIDS patients with CMV cerebritis, but not normal subjects, contained TGF-beta detected by immunoperoxidase staining. TGF-beta staining could be localized within or near astrocytes, some of which were infected with CMV. To determine whether CMV infection of astrocytes could induce production of TGF-beta, we incubated murine astrocytes with murine CMV in vitro. The infected astrocytes were assayed for TGF-beta mRNA, and the astrocyte culture supernatants were assayed for CMV and TGF-beta. It was found that the astrocytes were productively infected with the murine CMV, expressed TGF-beta mRNA, and secreted TGF-beta peptide.