L-Tryptophan, an essential amino acid, is readily converted to serotonin, which is thought to be important for expression of slow wave sleep and possibly rapid eye movement (REM) sleep. A vast but often confusing literature exists on L-tryptophan effects on inducing, maintaining, or altering sleep. In this study we measured the effects of L-tryptophan on objective (multiple sleep latency) and subjective [Stanford Sleepiness Scale (SSS)] measures of sleepiness and examined their relationship to blood L-tryptophan levels. Ten healthy volunteers (eight men and two women; mean +/- SD age 34 +/- 10 years) received placebo or 1.2 or 2.4 g or L-tryptophan on separate days in random double-blind fashion. Sleep latency and SSS were measured initially and at 60 and 120 min after ingestion. Blood and urine were collected at regular intervals. Compared with placebo both L-tryptophan doses reduced sleep latency at 1 h, with the reduction persisting at 2 h for the 2.4-g dose only (p less than 0.05). There was a positive correlation between subjective and objective sleepiness measures but only with the 2.4-g dose (rs = 0.76, p less than 0.01). There was a highly significant correlation between blood L-tryptophan and sleep latency at 0, 60, and 120 min in all subjects for all drug conditions (r = 0.276, df = 79, p = 0.013). Very small amounts of free L-tryptophan or its metabolites were found in the urine, with the exception of kynurenic acid. We conclude that L-tryptophan consistently reduced sleep latency in normals and that this correlates with blood levels.(ABSTRACT TRUNCATED AT 250 WORDS)