Clinical descriptions of acute or primary infection with the human immunodeficiency virus (HIV) are rare. Among cases previously reported, most describe an acute illness resembling infectious mononucleosis. We describe the case of a 32-year-old homosexual man with an acute illness associated with strong serologic evidence of a primary infection with HIV. This case illustrates two new clinical features: an acute, bilateral brachial neuritis, and a vesicular, pustular exanthematous and enanthematous rash. Studies of HIV-related serologic results show differential sensitivities for enzyme-linked immunosorbent assay, Western blot, immunofluorescence, and viral antigen techniques in the acute phase of HIV infection. There appears to be significant clinical heterogeneity of the acute phase of HIV infection.