The amino acid tryptophan (tryp) is a potent inhibitor of gastric emptying in both animals and humans. Animal studies suggest that this effect may be specific for the L-enantiomer. The effects of D- and L-tryptophan on gastric emptying, intragastric distribution and appetite in humans were evaluated. Ten volunteers ingested 300 mL of either L-tryp (50 mmol/L), D-tryp (50 mmol/L) or normal saline labelled with 99mTc sulfur colloid on three occasions, separated by between 3 and 7 days. Hunger and fullness were measured with a visual analogue scale at -2, 15, 30 and 60 min after ingestion of each drink. Saline emptied faster from the stomach than both L-tryp and D-tryp (P < 0.05) and D-tryp emptied faster than L-tryp (P < 0.005). Emptying from the proximal stomach was fastest for saline (P < 0.05) and faster for D-tryp than L-tryp (P < 0.005). Emptying from the distal stomach was faster for saline than both D- and L-tryp (P < 0.05). A reduction in hunger (P < 0.05) and a non-significant trend for an increase in fullness were observed after all three drinks. At 60 min, fullness was greater after L-tryp than after ingestion of D-tryp (P < 0.01). These observations indicate that the effect of tryptophan on gastric emptying in humans is stereospecific, consistent with the concept that stereospecific receptors for tryptophan exist in the human small intestine.