We examined 516G>T polymorphisms at the gene encoding the cytochrome P450 in 100 human immunodeficiency virus-positive subjects who were receiving efavirenz (EFV). Elevated plasma EFV concentrations were found in 40% of subjects with the polymorphic homozygous genotype and 19% of subjects with the heterozygous genotype. Conversely, 20% of subjects with the wild-type genotype had subtherapeutic concentrations of EFV. CYP2B6-516 genotyping may help to identify subjects who have plasma EFV concentrations that are outside of the therapeutic range.