The elimination kinetics of dyphylline were investigated in four uremic patients receiving chronic hemodialysis treatment. Dyphylline (1000 mg) was administered to each patient orally 2 hr before hemodialysis. Serial arterial and venous blood samples as well as outflowing dialysate samples were collected and analyzed by high-pressure liquid chromatography for dyphylline. The extraction efficiency of the hollow-fiber dialyzers averaged 44.6%. The mean dialysis clearance was 108.7 ml/min which compares favorably to the 57 ml/min metabolic clearance of the drug. A mean of 278.6 mg or 28.34% of the administered dose was recovered in the dialysate during the 4-hr dialysis interval. Half-lives for dyphylline during dialysis ranged from 3.43 to 7.62 hr. The off-dialysis half-lives for two of the four patients studied on a separate occasion were 10.6 and 13.2 hr. The overall clearance calculation projects an average half-life reduction of approximately 65% during hemodialysis. We conclude that dyphylline is dialyzable. Hemodialysis patients receiving dyphylline treatment may require a dosage regimen alteration. In addition, hemodialysis may be useful for the treatment of dyphylline overdose because of its effectiveness in accelerating the removal of the drug.