Efavirenz, a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, is a promising addition to the antiretroviral armamentarium. Efavirenz levels and HIV-1 RNA levels were measured in cerebrospinal fluid (CSF) and plasma of 10 HIV-1-infected patients taking efavirenz, 600 mg daily, in combination with other antiretroviral medications. Efavirenz was detected in the CSF at a mean concentration of 35.1 nM (range, 6. 6-58.9 nM), which was above the IC95 for wild-type HIV-1. The mean CSF-to-plasma ratio was 0.61% (range, 0.26%-0.99%). CSF HIV-1 RNA levels were ascertained in 9 of the patients; all were <400 copies/mL after a mean of 26 weeks on therapy. Eight of the 9 patients had no detectable virus in plasma. These results indicate that efavirenz is present in the CSF at low levels and is effective in suppressing CSF viral levels when used in combination therapy.