We investigated the effect of efavirenz treatment on the results of drug screening tests of urine samples obtained from 100 patients infected with human immunodeficiency virus. Of 50 patients who received efavirenz, 49 tested positive for benzodiazepines in > or =1 drug screening test, whereas of 50 patients who did not receive efavirenz, only 1 tested positive for benzodiazepines in > or =1 drug screening test. The major metabolite 8-hydroxy-efavirenz is responsible for this cross-reactivity.