Muscle potassium content and supplementation with potassium gluconate were evaluated in normokalemic cats with chronic renal failure (CRF). Affected cats received standard medical therapy for renal failure and either placebo (sodium gluconate) or potassium gluconate. At the beginning of the study and after 6 months of supplementation, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated using 3H-inulin and 14C-tetraethylammonium bromide (TEA) clearances. Muscle potassium content was determined in biopsy specimens using atomic absorption spectroscopy. Muscle biopsy samples obtained from cats with CRF before treatment had significantly lower muscle potassium content than did those from normal control cats. Over the 6-month period of supplementation, muscle potassium content increased both in cats with CRF that received potassium gluconate and in those that received placebo (sodium gluconate). Serum potassium concentration and fractional excretion of potassium remained relatively unchanged in both groups of cats throughout the treatment period. There were no significant differences in the percentage change in GFR and ERPF between treatment groups over the 6-month time period. Median values for pH, HCO3-, and total CO2 at 6 months were higher than baseline in the potassium gluconate group but lower than baseline in the sodium gluconate group.