We tested the hypothesis that K(+) intake is sensed by putative K(+) sensors in the splanchnic areas, and renal K(+) handling is regulated by this signal. K(+) was infused for 2 h into overnight-fasted rats via the jugular vein (systemic infusion), hepatic portal vein (intraportal infusion), or stomach (intragastric infusion) (n = 5 each), and plasma K(+) concentration ([K(+)]) and renal K(+) excretion were measured during the 2-h preinfusion, 2-h K(+) infusion, and 3-h washout periods. During systemic K(+) infusion, plasma [K(+)] increased by approximately 1.3 mM (P < 0.05), and, on cessation of the K(+) infusion, plasma [K(+)] fell to the preinfusion level within 1-2 h. Renal K(+) excretion changed in proportion to the changes in plasma [K(+)]. During intraportal or intragastric K(+) infusion, plasma [K(+)] and renal K(+) excretion profiles were similar to those with systemic infusion. The effects of K(+) infusions via the different routes (n = 5 or 6 each) were also studied during simultaneous feeding of overnight-fasted rats with a K(+)-deficient diet. During the meal, intraportal infusion resulted in increases in plasma [K(+)] similar to those with the systemic K(+) infusion, while intragastric K(+) infusion did not significantly increase plasma [K(+)]. Thus, when the intragastric K(+) infusion was combined with a meal, there was marked enhancement of clearance of the K(+) infused, which was associated with an apparent increase in renal efficiency of K(+) excretion. These data suggest that there may be a gut factor that enhances renal efficiency of K(+) excretion during meal (or dietary K(+)) intake.