5-Hydroxytryptamine is a mediator in cholera toxin-induced hypersecretion in the small intestine. Our hypothesis is that the hypersecretion induced by 5-hydroxytryptamine in the small intestine decreases with increasing age and in an aboral direction in the small intestine. In vivo, measuring accumulated fluid in ligated loops, the apparent maximal efficacy of the 5-hydroxytryptamine-induced jejunal secretion in pig neonates was 4.8 +/- 1.1 mg x mg(-1) dry loop x 45 min(-1). The apparent maximal efficacy decreased by 23% and 63% in young and adult pigs, respectively, compared with neonates. In vitro, measuring changes in short-circuit current in Ussing chambers, the apparent maximal efficacy was 66.7 +/- 4.8 micronA x cm(-2) in neonates and was reduced by 30% and 57% in young and adult pigs, respectively. Young pigs were used in the segmental study. The apparent maximal efficacy in vivo was 3.7 +/- 0.5 mg x mg(-1) dry loop and decreased by 22% and 56% in the mid and distal small intestine, respectively. By contrast, in vitro the apparent maximal efficacy was elevated by 56% to 72.0 +/- 5.0 micronA x cm(-2) in the distal compared with the proximal part. In conclusion, the secretory response to 5-hydroxytryptamine in pig small intestine decreases with increasing age and in the aboral direction according to in vivo results. We suggest that the decrease in sensitivity to 5-hydroxytryptamine can explain a part of the reduced secretory response to cholera toxin with age and in the aboral direction of the small intestine.