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⁺] and renal K⁺ excretion were measured during the 2-h pre-infusion, 2-h K⁺ infusion, and 3-h washout periods. During systemic K⁺ infusion, plasma [K⁺] increased by ~1.3 mM (P<0.05), and, upon cessation of the K⁺ infusion, plasma [K⁺] fell to the pre-infusion level within 1-2 hours. 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.