The transforming growth factor-beta family of polypeptides includes three related isoforms with pervasive effects on immune system function. In this study, the authors evaluated human brains with human immunodeficiency virus (HIV)-1 encephalitis for transforming growth factor beta (TGF beta)1, TGF beta 2, and TGF beta 3 immunoreactivity using isoform-specific polyclonal antibodies and avidin-biotin immunohistochemistry. Normal brains and those with progressive multifocal leukoencephalopathy, toxoplasma encephalitis, and cryptococcal meningitis were used as controls. In normal controls, TGF beta 1, TGF beta 2, and TGF beta 3 immunoreactivity were confined to arachnoid cells and blood vessels. In 9 of 10 cases of HIV-1 encephalitis, all three isoforms were also detected in arachnoid cells. In addition, variable, predominantly TGF beta 2 and TGF beta 3 immunoreactivity were also detected in reactive astrocytes and mononuclear cells of white matter lesions. Extensive TGF beta 3 immunoreactivity was also detected in multinucleated giant cells in one case. In a case of cryptococcal meningitis, all three isoforms were detected in arachnoid cells and macrophages. Lesions of progressive multifocal leukoencephalopathy and toxoplasma encephalitis also exhibited TGF beta 1, TGF beta 2, and TGF beta 3 immunostaining in reactive astrocytes. These findings suggest that TGF beta isoforms are present in HIV-1 encephalitis and may participate in the pathogenesis of this and other inflammatory central nervous system (CNS) lesions associated with acquired immunodeficiency syndrome (AIDS). Copyright (C) 1996 by W.B. Saunders Company.