Neonatal mice with cystic fibrosis (CF) exhibit a very high mortality due to intestinal obstruction localized primarily to the ileum and colon. It has been hypothesized that lack of Cl(-) secretion and possibly elevated Na(+) absorption contribute to the gut problems in CF neonates. Therefore, intestines (ileum, proximal colon, and distal colon) from normal and CF day-old mouse pups were studied on ultra-small-aperture (0.0135 cm(2)) Ussing chambers. All three regions of the normal neonatal intestine responded to forskolin with an increase in short-circuit current, which was completely absent in the CF intestine. The neonatal distal colon exhibited a high rate of amiloride-sensitive electrogenic Na(+) absorption, which did not differ between the normal and CF preparations. The ileum and proximal colon of both genotypes exhibited a small but significant electrogenic Na(+) absorption. The neonatal proximal colon and ileum also exhibited electrogenic Na(+)-glucose cotransport, which was significantly greater in the normal compared with the CF ileum. In addition, all three intestinal regions exhibited electrogenic Na(+)-alanine cotransport, which was significantly reduced in two of the regions of the CF neonatal intestine. It is speculated that: 1) the reduced rate of Na(+)-nutrient cotransport in the CF intestine contributes to the lower rate of growth in CF pups, whereas 2) the elevated electrogenic Na(+) absorption in the neonatal intestine, coupled with an inability to secrete Cl(-), contributes to the intestinal obstruction in the CF pups.