There are typical morphological indicators of tubular defects during the administration of ciclosporin A (CSA). Distal tubular function remains unclear although hyperkalemia is a common clinical feature in these patients. We performed renal function studies 3 months after renal transplantation on 35 patients (group 1) treated with CSA. The results were compared to those of a control group consisting of 15 patients transplanted earlier and treated with azathioprine (group 2). Only patients with stable renal function (creatinine less than or equal to 2.0 mg/dl) entered the investigation consisting of: inulin (In) clearance; p-aminohippuric acid (PAH) clearance; ammonium chloride loading; sodium sulfate loading, and sodium bicarbonate loading. Plasma renin activity and aldosterone were measured basally and after stimulation with 40 mg i.v. furosemide. Clearances of In and PAH were significantly impaired during the administration of CSA. Group 1: CIn 73.3 +/- 8.7 ml/min/1.73 m2 (p less than 0.01), CPAH 263 +/- 58.3 ml/min/1.73 m2 (p less than 0.01); group 2: CIn 89.6 +/- 19.1 ml/min/1.73 m2, CPAH 338.7 +/- 63.5 ml/min/1.73 m2. Incomplete distal tubular acidosis could be demonstrated in 8 patients from group 1 but none of group 2. Hyporeninemic hypoaldosteronism could be demonstrated in 4 patients during the administration of CSA. CSA in therapeutic doses significantly impairs renal perfusion, glomerular filtration, distal acidification and the renin-aldosterone axis.