In uremic patients the serum protein binding of phenylbutazone was significantly decreased. The concentration of the dialyzable drug estimated by equilibrium dialysis was increased by 117-1100% (mean +/-SD = 502 +/- 236%). No correlation exists between the serum protein binding of phenylbutazone and the concentration of serum albumin, urea and creatinine. The serum protein binding of glymidine was also decreased in the uremic patients (dialyzable fraction increased by 214%). The apparent plasma levels of phenylbutazone immediately after its ingestion (600 mg per os) were decreased in uremic patients (44.5 +/- 11 mug/ml) in comparison with healthy subjects (66.3 +/- 17.3 mug/ml). The half life of phenylbutazone was decreased in the uremic patients (41.7 +/- 12.4 hr) in comparison with healthy volunteers (58.9 +/- 14.9 hr). It is suggested that the accelerated elimination of phenylbutazone in uremic patients is caused by an altered distribution of the drug caused by its decreased serum protein binding.