We retrospectively assessed the frequency and clinical characteristics of headache occurring in human immunodeficiency virus (HIV)-infected patients in whom we had excluded all other causes, and determined the frequency of a similar headache in an HIV-negative group. Over a 1-year period, the HIV-related headache occurred in 2.8% of total admissions to the HIV service as opposed to 0.2% of admissions to the neurology service. The affected patients had advanced HIV infection (CD4+ cell count = 58.9 +/- 80.3; normal, > 500 x 10(-6)/l). The headache had features similar to those ascribed to HIV aseptic meningitis and was not related to the presence of AIDS dementia complex or its subsequent development over a 6-month follow-up. We propose that this is a distinct clinical entity related to HIV infection that is similar, if not identical, to HIV aseptic meningitis except for the lack of a CSF pleocytosis, probably reflecting the lymphocyte depletion that is characteristic of the more advanced state of HIV infection.