The polymerase chain reaction (PCR) was used to detect HIV-1 sequences (gag,pol, andenv) in the cerebrospinal fluid (CSF) and serum samples from 53 HIV-1-positive patients and the results correlated with clinical evidence of neurological disease. Twenty-three out of 24 patients with neurological disease had HIV-1-specific sequences in CSF compared with four out of 20 asymptomatic patients who had no evidence of neurological involvement. The detection of HIV RNA sequences by PCR in the CSF of HIV-positive patients may provide early, rapid and direct evidence of neurological involvement in asymptomatic subjects.