The effects of high doses of frusemide on plasma and muscle electrolyte composition were investigated in 20 patients with chronic renal failure (CRF), in 5 of them complicated by superimposed cardiac decompensation (CRF + CD). In patients with uncomplicated CRF, short-term frusemide therapy resulted in a decrease of muscle water content, while no significant effect on muscle electrolyte and protein nitrogen contents was observed. On the contrary, in patients with CRF + CD, muscle water (both in the extracellular and intracellular phases), sodium and chloride concentrations fell significantly as a result of frusemide therapy. Muscle potassium remained unchanged, even if related to the cell protein content, in both groups of patients. These results support the conclusion that, in patients with uncomplicated CRF, short-term frusemide therapy acts primarily on plasma and extracellular volume with little or no modification of intracellular fluids and tissue electrolyte composition.