Escherichia coli which elaborate heat stable enterotoxin (ST) are a major cause of endemic diarrhea in infants. The reason(s) for this increased susceptibility of infants to ST-mediated diarrhea is unknown. We investigated the possibility that the immature (14 and 21 day old) rat small intestine is more sensitive to ST than is the adult. Initially we found there was a 600-fold increased jejunal sensitivity to ST in the immature animals as measured by dose required for half maximal secretion. Also there was a greater jejunal secretory response in the immature animals (14 > 21 days old > adult). To determine the cause for this increased sensitivity and secretory response to ST, we examined: 1) binding characteristics of 125I-ST to brush border membrane (BBM) receptors and 2) membrane bound guanylate cyclase activation by ST in both immature and adult rats. Our findings demonstrate that more ST receptors are present in jejunal BBM from 14- and 21-day-old rats than in jejunal BBM from adult rats (2.34 ± 0.18, 2.85 ± 0.82, and 0.79 ± 0.13 X 1012 receptors/mg BBM protein, respectively), while the affinity of the BBM receptor for ST is similar at all three ages in both jejunum and ileum. Furthermore, both the jejunum and ileum of the rats of all three ages revealed an equal sensitivity of guanylate cyclase to activation by ST. These findings suggest that the increased number of jejunal receptors in the immature rat may, in part, explain the increased sensitivity and secretory response observed in vivo. © 1986 International Pediatric Research Foundation, Inc.