The possibility that efferent factors in addition to aldosterone and plasma K may mediate the renal response to large variations in K intake in sheep was explored in experiments on four mature ewes. K supplementation of a normal diet provided a total K intake of 1,300-1,500 meq/day for 3 days and produced a high K excretion (737 +/- 34 mu eq/min) with plasma K 4.67 +/- 0.07 meq/liter. K deprivation by 83 h of fasting produced low K excretion (48 +/- 10 mu eq/min) with plasma K 3.60 +/- 0.14 meq/liter. Additional treatments during both K-supplemented and K-deprived states included: raising plasma K through the range 4-7 meq/liter by intravenous infusion of 45 meq KCl in 30 min; intravenous infusion of aldosterone (20 micrograms/h) or of an aldosterone antagonist, potassium canrenoate (100 mg/h). Na supplementation during fasting was by rumen infusion of Na acetate-Na propionate (1,000 meq Na/day). Results showed that the increase in plasma K during intravenous K infusion directly elevated K excretion, that aldosterone enhanced and canrenoate depressed the kaliuretic effect of K infusion, and that Na loading during fasting enhanced the kaliuretic effect of aldosterone. Comparisons, made at the same level of plasma K, indicated that differences in plasma K, aldosterone, or Na excretion were not sufficient individually or in combination to account for the large differences of 350-1,150 mu eq/min in K excretion that existed between K-supplemented and K-deprived states. Unidentified kaliuretic regulatory factors appear to play a major role in the homeostatic control of K excretion in sheep under the circumstances of these experiments.