Human immunodeficiency virus type 1 (HIV-1) RNA can be detected in the cerebrospinal fluid (CSF) of 75-90% of all HIV-infected patients. However, it is not yet known which factors influence the amount of HIV-1 in the CSF, either qualitatively or quantitatively. We have analysed HIV-1 RNA in CSF samples from 24 HIV-infected patients using zidovudine who underwent lumbar puncture in order to establish a diagnosis for a neurological disorder. Several factors were examined for possible correlation with the amount of HIV-1 RNA in the CSF: age, gender, the medical indication for lumbar puncture, the most recent CD4 cell count in blood, zidovudine dose, duration of treatment with zidovudine, the zidovudine concentration in plasma and CSF, and the total protein concentration in plasma and CSF. The only statistically significant factor was the total protein level in the CSF, which showed a positive relation with the amount of HIV-1 RNA in the CSF. This study indicates that increased levels of HIV-1 RNA in the CSF of neurologically symptomatic patients are the result of damage to the blood-brain barrier.