Gastrointestinal peptides, including insulin, glucagon and glucose-dependent insulinotropic polypeptide (GIP) have previously been reported in salivary glands. Recent evidence has suggested they might influence postprandial macronutrient metabolism. This study therefore investigated and compared postprandial hormone concentrations in saliva and plasma to determine whether their secretion was influenced by oral food stimuli. In a within-subject randomised cross-over comparison of hormone concentrations in plasma and saliva following a mixed meal, 12 subjects were given two 1708 kJ mixed meals. On one occasion the meal was chewed and swallowed (swallowed meal), on the other it was chewed and expectorated (sham-fed meal). Salivary and plasma levels of immunoreactive insulin, GIP and glucagon-like peptide-1 (GLP-1), total protein, -amylase, glucose and nonesterified fatty acid were measured before and for 90 min following the meals. Saliva total protein and -amylase rose following both meals, indicating that the stimulus for salivary protein release is related to the presence of food in the mouth. GLP-1 was not detected in saliva. Fasting salivary insulin levels were lower in saliva than plasma (28 6 vs 40 25 pmol/l respectively). Both increased following the swallowed meal but the rise in saliva was slower and less marked than in plasma (peak levels 96 18 and 270 66 pmol/l for saliva and plasma respectively, P<0·01). Both were unchanged following the sham-fed meal. GIP was detected in saliva. Fasting GIP levels were significantly higher in saliva than plasma (183 23 compared with 20 7 pmol/l, P<0·01). They decreased in saliva following both swallowed and sham-fed meals to nadirs of 117 17 and 71 12 pmol/l respectively, but rose following the swallowed meal to peak levels of 268 66 pmol/l. These findings are consistent with insulin in saliva being an ultrafiltrate of that circulating in blood, but GIP in saliva being the product of local salivary gland synthesis, whose secretion is influenced, directly or indirectly, by oral stimuli. The function of salivary GIP is unknown, but we speculate that it may play a role in the regulation of gastric acid secretion in the fasting state.