The effect of splanchnic nerve activation on intestinal fluid transport and intramural blood flow distribution was examined in the cat. Previous reports from our laboratory have demonstrated that splanchnic nerve activation increases fluid absorption. The present study was performed to elucidate the mechanisms behind this effect. The results showed an increase in net sodium and chloride transport on splanchnic nerve activation whether intestinal blood flow decreased or not. The effect on sodium transport was due to a decrease in lumen to tissue flux. The effect could not be explained by a decrease in local blood flow, as it was present despite constant blood flow in both the villous and crypt regions. No change was seen in the villous osmolality gradient on splanchnic nerve activation. On the basis of these findings, it is proposed that the in vivo effect of splanchnic nerve activation is due to a decrease in fluid and electrolyte secretion, probably occurring in the intestinal crypts.