The patterns of storage and release of serotonin found in the enterochromaffin cells of the intestinal mucosa suggest that this hormone may be an important modulator of intestinal functions. Serotonin has been shown to produce secretion of water and electrolytes in rabbit ileum, but the hormone does not appear to interact significantly with other transport processes. The aim of the present study was to determine the effect of serotonin on D-galactose absorption in rabbit jejunum. The results obtained show that serotonin (10(-8) and 10(-6)M) partially reduced (by 20 and 40% respectively) D-galactose uptake across the mucosal border. This effect was concentration-dependent, and it seemed to be caused by the inhibition of Na+-dependent sugar transport. Methysergide, an antagonist of serotonin which binds with receptor 2 of serotonin, blocked the effect of serotonin. These findings suggest that serotonin may act as a regulator of sugar intestinal absorption, and that this serotonin regulation could be mediated by a direct or indirect action of the complex serotonin-receptor, which may inhibit the Na+-dependent transport system of sugars located in the brush-border membrane.