Background. Chronic metabolic acidosis (CMA) in normal adults results in complex endocrine and metabolic alterations including growth hormone (GH) insensitivity, hypothyroidism, hyperglucocorticoidism, hypoalbuminaemia and loss of protein stores. Similar alterations occur in chronic renal failure, a prototypical state of CMA. We evaluated whether metabolic acidosis contributes to the endocrine and metabolic alterations characteristic of end-stage renal disease. Methods. We treated 14 chronic haemodialysis patients with daily oral Na-citrate for 4 weeks, yielding a steady-state pre-dialytic plasma bicarbonate concentration of 26.7 mmol/l, followed by 4 weeks of equimolar Na-chloride, yielding a steady-state pre-dialytic plasma bicarbonate of 20.2 mmol/l. Results. Blood pressure, body weight and dialysis adequacy were equivalent in the two protocols. Na-citrate treatment corrected CMA, improved GH insensitivity, increased and normalized plasma free T3 concentration, and improved plasma albumin. Correction of CMA had no significant effect on measured cytokines (interleukin-1β and -6, tumour necrosis factor-α) or acute phase reactants (C-reactive protein, serum amyloid A, α2-macroglobulin). Conclusion. CMA contributes to the derangements of the growth and thyroid hormone axes and to hypoalbuminaemia, but is not a modulator of systemic inflammation in dialysis patients. Correcting CMA may improve nutritional and metabolic parameters and thus lower morbidity and mortalit