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CD27 is a member of the tumor necrosis factor receptor superfamily that is expressed primarily on T cells, as well as on subsets of B cells and NK cells. CD70, which is expressed on activated B and T cells, but not on resting lymphocytes, is a ligand for CD27. Cell surface CD27 can be proteolytically cleaved to produce a 32-kDa soluble CD27 (sCD27) molecule. Elevated levels of sCD27 are seen in a number of disease states and malignancies. Although it has been reported that cerebrospinal fluid sCD27 levels were elevated in people who had AIDS dementia, little is known about CD27 expression in HIV disease. To determine if sCD27 levels were elevated in those with HIV infection, and/or in those with AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL), sCD27 levels were measured in HIV-negative and HIV-positive subjects as well as in people who developed AIDS-NHL. Serum sCD27 levels were seen to be elevated in HIV+ subjects. Furthermore, sCD27 levels were particularly elevated in those subjects who went on to develop AIDS-NHL, with serum sCD27 levels in AIDS-NHL subjects being significantly higher than those in HIV+ subjects who did not develop lymphoma. Most AIDS-NHL cell lines and primary AIDS-NHL tumor specimens expressed both CD27 and its ligand, CD70. The proportion of circulating B cells that expressed cell surface CD27 was substantially reduced in those with HIV infection, and B cells from HIV-infected subjects produced decreased levels of sCD27 in culture. Together, these results indicate that CD27/sCD27 expression is abnormal in HIV infection and suggest that this molecule merits further examination as a potential marker for AIDS-NHL., (Copyright 1999 Academic Press.)