Eight healthy male subjects received single 2-mg oral doses of lorazepam containing 24 muCi/mg of 2-14C-lorazepam. Multiple venous blood samples were drawn during the first 96 hr after the dose, and all urine and stool were collected for 120 hr after dosing. Concentrations of lorazepam and its metabolites in body fluids were determined by appropriate analytic techniques. Following a lag time, lorazepam was absorbed with an apparent first-order half-life of 15 min. The peak plasma concentration was 16.9 ng/ml, measured in the pooled sample drawn 2 hr after the dose, This corresponded to the time at which clinical effects appeared to be maximal. The apparent elimination half-life of lorazepam was about 12 hr. Biotransformation to a pharmacologically inactive glucuronide metabolite appeared to be the major mechanism of lorazepam clearance. A mean of 88% of administered radioactivity was recovered in urine, and 7% was recovered in stool. Lorazepam glucuronide comprised 86% of urinary reactivity; its renal clearance was 37 ml/min. Other identified metabolites included hydroxylorazepam, a quinazolinone derivative, and a quinazoline carboxylic acid; all of these were quantitatively minor.