In a randomized cross-over study healthy non-obese male human subjects received standardized isocaloric, isovolumetric meals consisting of either carbohydrate, protein or fat and a non-caloric control meal consisting of an equal volume of water. Peripheral venous plasma concentrations of calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and peptide YY (PYY) were measured pre- and postprandially. Plasma CGRP concentrations were lowered following the protein meal and following the fat meal, but remained unaltered after carbohydrate or water ingestion. Plasma VIP concentrations increased slightly following the carbohydrate meal and following water loading. The PYY concentrations increased after the protein and the carbohydrate meal and a slight rise was observed following fat ingestion. Water loading did not affect the plasma level of PYY. We conclude that the postprandial peripheral plasma concentrations of CGRP, VIP and PYY are dependent on the caloric meal composition. The VIP, but not the CGRP and PYY concentrations seem to be influenced by gastric distension. The physiological significance of the postprandial alterations in peripheral concentrations of these peptides is at present uncertain.