Muscle content of water and electrolytes (needle biopsy), intraarterial BP and cardiac output (dye dilution technique) were measured in 12 patients with essential hypertension before and after 4 months of mefruside therapy (25 mg/day). Before therapy there were no significant differences in muscle tissue electrolyte and water content compared with normotensive subjects. No correlation was found between central hemodynamic variables and the electrolyte and water content of muscle tissue either before or after therapy. After 4 months of mefruside therapy, muscle tissue water showed a mean decrease which was not significant. Serum potassium and muscle potassium content decreased significantly but there was no significant change in intracellular potassium concentration. Intracellular sodium concentration increased significantly, while muscle sodium content showed a mean increase which was not statistically significant. The change in intracellular sodium concentration showed a significant negative correlation with the decrease in mean arterial BP. The change in total cellular water content showed a significant negative correlation to the changes in total peripheral vascular resistance. Saluretic therapy seems to induce counterregulatory mechanisms that interfere with the hypotensive effect.