The postnatal development of atrial natriuretic peptide (ANP) stimulus-secretion coupling was examined in rabbit ileum. A positive correlation between age and ANP-induced secretory responsiveness was observed. The short circuit current (Isc) response in 14-day animals was significantly (p < 0.05) less than that seen in 21-day, 28-day and adult animals. Animals at 21 days of age were less responsive (p < 0.05) than either 28-day or adult animals which did not differ. The Isc response of infant animals (day 14) to the Cl- secretagogue 3-isobutyl-1-methylxanthine was blunted in the infant, as was the response to electrical field stimulation. The infant animals had higher basal levels of mucosal cGMP, but were still able to respond to ANP with an elevation in cGMP. The ability of the immature ileum to generate the second messenger molecule cGMP in response to ANP, but not to produce an appropriate Isc response to ANP, indicates infant animals possess underdeveloped secretory mechanisms and lack the ability to effectively couple secretory stimuli to a secretory response.