The aim of this study was to test whether atrial natriuretic factor (ANF) exerts any effect on human intestinal ion transport, and the porcine intestine was used as a positive control of ANF's effects. Tissues from human proximal (n = 6) and distal (n = 6) colons, and from distal ileum (n = 6) were mounted in Ussing chambers, and short circuit current (Isc) was measured subsequent to serosal application of ANF (10(-6) M), 8-Br-cyclic guanosine monophosphate (8-Br-cGMP) (10(-4) M), and theophylline (10(-2) M). ANF did not affect Isc whereas 8-Br-cGMP increased Isc by 28 (8-53), 16 (3-36), and 16 (5-41) microA cm-2 in the distal colon (DC), proximal colon (PC) and distal ileum (DI), respectively. Likewise, transepithelial potential difference (PD) became more negative by 5.0 (0.6-8.9), 2.5 (0.4-4.0) and 0.9 (0.3-2.3) mV in DC, PC, and DI, respectively, subsequent to addition of 8-Br-cGMP. Isc and PD were further increased by theophylline. Additional radio-isotope flux studies in human colon revealed that ANF did not affect electroneutral sodium and chloride transport either. For comparison, ANF (10(-6) M) was administered to large intestinal tissues from young pigs in which ANF induced a significant increase in Isc which was comparable to the 8-Br-cGMP response in humans. The porcine Isc response was partly inhibited by chloride-free solution on the serosal side, by serosal application of bumetanide (10(-4) M) and BaCl2 (10(-3) M), and mucosal application of the chloride-channel blocker diphenylamine-2-carboxylate (DPC) (10(-3) M). Mucosal amiloride (10(-5) M) pre-treatment reduced baseline Isc but did not affect the porcine intestinal Isc response to ANF. In vitro radio-autography demonstrated specific binding sites for ANF in porcine distal colon, whereas no apparent labelling was observed in human distal colon. These findings suggest that the lack of effect of ANF on sodium and chloride transport in human distal ileum and colon is probably due to lack of ANF receptors. In the porcine intestine, however, the Isc response induced by ANF seems to involve stimulation of electrogenic chloride secretion, whereas electrogenic sodium absorption seems unaffected.