We compared plasma ANF concentration in 5 diabetic-uremics with combined sympathetic-parasympathetic dysfunction with that in 9 uremic patients without autonomic impairment. Symptomatic dialysis hypotension was a major clinical problem in all diabetic-uremics. In the volume-expanded state, ANF was almost twice as high (p less than 0.025) in diabetic-uremics than in control uremics (152 +/- 29 vs 84 +/- 10 pg/ml) in the face of similar right atrial pressure (14 +/- 3 vs 12 +/- 1 cm H2O). After isolated ultrafiltration, ANF fell significantly in both groups remaining slightly (NS) higher in diabetic-uremics. The slope of the relationship between ANF and right atrial pressure was significantly (p less than 0.01) steeper in diabetic-uremics than in control uremics. The data indicate that autonomic failure amplifies the effect of atrial stretching on plasma ANF in diabetic-uremics on chronic hemodialysis treatment.