Levels of whole blood serotonin and tryptophan were measured in 11 human subjects after the consumption of a meal. Blood samples were obtained at 30 and 15 min before the meal and at 15, 30, and 60 min postcibal. One-hour urine specimens were collected for 5 subjects at 0, 60, and 120 min. Whole blood serotonin and tryptophan and urinary 5-hydroxyindoleacetic acid were measured using specific high-performance liquid chromatographic methods. A precibal mean (+/- SEM) serotonin level of 136 +/- 8 ng/ml (n = 22) was observed; means at 15, 30, and 60 min after the meal were 138 +/- 20 ng/ml (n = 9), 145 +/- 18 ng/ml (n = 11), and 138 +/- 16 ng/ml (n = 11), respectively. At no time were postcibal levels of whole blood serotonin significantly higher than baseline levels (paired t-test). Urinary excretion of 5-hydroxyindoleacetic acid also was unchanged; mean hourly rates were 230 +/- 23 micrograms/h before the meal, and 196 +/- 17 micrograms/h and 190 +/- 33 micrograms/h (n = 5) during the first and second hour postcibal, respectively. The absence of a postcibal increase of serotonin in circulating whole blood indicates that serotonin is probably not a human gastrointestinal hormone in the usual sense.