Cerebrospinal fluid (CSF) sulfatide concentrations were analyzed in 18 patients with asymptomatic HIV-1 infection, in 16 patients with AIDS who were free from opportunistic infections in the central nervous system (CNS), in 12 HIV-1-infected patients with opportunistic CNS infections or lymphoma, and in 19 HIV-negative controls, by thin-layer chromatography overlay technique using an antisulfatide antibody to estimate the metabolic turnover of myelin. The majority of asymptomatic HIV-1-infected patients had normal CSF sulfatide concentrations, but the mean CSF sulfatide concentration was still elevated compared to that in HIV-negative controls (152 compared to 99 nmol/liter, p < 0.05). The CSF sulfatide concentrations in the AIDS group (mean 395 nmol/liter) were significantly increased compared to those in asymptomatic HIV-1-infected patients (p < 0.01) and in HIV-negative controls (p < 0.001), but did not differ significantly between patients with and without dementia. Increased CSF sulfatide concentrations were also found in patients with opportunistic infection or lymphoma in the CNS. In the entire study population, the sulfatide levels were associated with blood-brain barrier function, but not with intrathecal immunoglobulin production or with positive HIV isolations from CSF. Thus, signs of white matter changes, measured as increased CSF sulfatide concentrations, could be found in some asymptomatic HIV-1-infected patients, but the highest levels were seen in patients with AIDS.