To investigate whether the contact between blood and dialysis membranes might induce muscle protein degradation, the exchange of free amino acids across leg tissues was measured by catheterization technique in three groups of healthy subjects before and after a 150 minute sham-hemodialysis procedure (SHDP), that is, in vivo passage of blood (100 ml/min) through a dialyzer but with no circulating dialysate. Dialyzers with either regenerated cellulose membrane (group CU, N = 10 and group CU-IND, N = 6) or polyacrylonitrile membrane (group AN, N = 8) were used in group CU-IND indomethacin was administered before (100 mg) and at the end (50 mg) of SHDP. Leg blood flow was measured by venous occlusion plethysmography. In group CU net leg release of tyrosine and phenylalanine increased from 3.4 +/- 0.8 and 3.6 +/- 0.8 nmol/min/100 g tissue, respectively, before SHDP to 7.8 +/- 1.8 and 8.3 +/- 1.8 nmol/min/100 g tissue, respectively, at 345 minutes after the start of SHDP (P less than 0.01). The total release of all measured amino acids increased from 148 +/- 31 to 309 +/- 50 nmol/min/100 g tissue (P less than 0.01). The results indicate that interaction between blood and regenerated cellulose membranes leads to accelerated net protein breakdown. In group CU-IND no change in leg amino acid release was observed following SHDP, suggesting that the increased net protein catabolism is mediated by prostaglandins. Sham hemodialysis using AN membranes did not result in increased amino acid efflux from leg tissues, implying that the protein catabolic effect of blood-membrane contact depends on the biochemical properties of dialyser.