The aim of this study was to investigate the skeletal muscle sodium/potassium (Na/K) ratio in acromegaly before and 1 year after trans-sphenoidal removal of a growth hormone (GH)-secreting pituitary adenoma. Muscle biopsies were taken and skeletal muscle electrolytes, body composition, glucose, insulin and blood pressure were studied. Fasting blood glucose and plasma insulin levels, but not blood pressure, were higher in acromegalic patients (N = 9) than in controls (N = 6). The skeletal muscle potassium content was higher (p < 0.01) but the sodium content and the Na/K ratio were lower (p < 0.05 and p < 0.001, respectively) in untreated patients with acromegaly as compared to weight-matched healthy controls. Elevated GH, glucose and insulin levels normalized after surgery. Blood pressure remained unchanged. The total body potassium content, the lean body mass and the total body water content decreased and the body fat content increased while the body weight was unchanged. The skeletal muscle potassium content decreased from [medium (range)] 9.8 (9.2-11.5) to 7.7 (5.7-9.5) mmol/100 g wet wt (p < 0.001). The skeletal muscle sodium content increased from 2.8 (2.5-3.9) to 5.1 (4.3-6.7) mmol/100 g wet wt (p < 0.001) and the Na/K ratio increased from 0.28 (0.26-0.38) to 0.56 (0.51-1.18) (p < 0.001) after surgery, which is a higher level than the controls with a Na/K ratio of 0.47 (0.39-0.84) (p < 0.01). These changes seem to be mediated by a decreased GH effect on the Na/K pump after successful trans-sphenoidal surgery in acromegaly.