Serum theophylline and metabolites (methyluric acids, mono- and dimethyl xanthines) concentrations from uremic patients, either with end-stage renal failure or on peritoneal dialysis or maintenance hemodialysis, were investigated by HPLC and compared with those obtained in non-uremic subjects. We conclude that in uremic patients serum theophylline metabolites, particularly serum 1,3-dimethyluric acid, are significantly higher than in non-uremic subjects even when serum theophylline is lower. A slight increase in the free fractions of serum theophylline was also observed in these patients. All these findings could explain the toxicity signs noted in some patients with chronic renal failure and treated with very low doses of theophylline.