Extracellular [K⁺] is closely regulated by the concerted regulatory responses of kidney and muscle. This study aimed to define the responses activated when dietary K⁺ was moderately reduced from control (1.0% K⁺) diet to 0.33% K⁺ diet for 15 days. Although body weight and baseline plasma [K⁺] (4.0 mM) was not reduced in the 0.33%K⁺ group, regulatory responses to conserve plasma [K⁺] were evident in both muscle and kidney. Insulin stimulated clearance of K⁺ from the plasma was estimated in vivo in conscious rats with tail venous and arterial cannulas. During infusion of insulin (50 mU kg-1 min-1) plasma [K⁺] fell to 3.2 ± 0.1 mM in 1.0% K⁺ group and to only 3.5 ± 0.1 mM in the 0.33% K⁺ group (p<0.01)with no reduction in urinary K⁺ excretion, evidence for insulin resistance to cellular K⁺ uptake. The insulin stimulated cellular K⁺ uptake was quantitated by measuring K⁺ infusion necessary to clamp plasma K⁺ at baseline (Kinf, µmol/(kg.min)) during insulin (5mU kg-1 min-1) infusion: 9.7 ±1.5 in 1% K⁺ diet blunted to 5.2 ± 1.7 in 0.33% K⁺ diet (p<0.001). Muscle [K⁺] and Na,K-ATPase activity and abundance were unchanged during 0.33%K⁺ diet. Renal excretion, measured overnight in metabolic cages, was reduced 80%: 117.6 ± 10.5 µmol/hr per animal (1% K⁺ diet) to 24.2 ± 1.7 µmol/hr per animal (0.33% K⁺ diet)(p<0.001). There was no significant change in total abundance of key renal K⁺ transporters but a 50% increases in both renal protein tyrosine kinase cSrc abundance and ROMK phosphorylation in the 0.33% K⁺ vs 1% K⁺ diet group, previously established to be associated with internalization of ROMK. These results indicate that plasma [K⁺] can be maintained during modest K⁺ restriction due to a decrease in insulin-stimulated cellular K⁺ uptake as well as renal K⁺ conservation mediated by inactivation of ROMK, both without a detectable change in plasma [K⁺]. The error signals inciting and maintaining these responses remain to be identified.