Free radical attack upon uric acid (UA) nonenzymatically generates allantoin (ALT), and the presence of ALT in human plasma suggests free radical intervention within the body. To assess this possibility, we determined plasma ALT in patients with chronic renal failure (CRF) and some other diseases by high-performance liquid-chromatography (HPLC). Heparinized blood samples were obtained from 15 healthy controls, CRF patients under conservative management (n = 13) or hemodialysis (HD) treatment (n = 8) and patients with gout (n = 11) or rheumatoid arthritis (RA, n = 13). Although not seen in normal plasma samples, ALT was detected in 63% and 31% of patients receiving HD and conservative treatment, respectively. The plasma ALT level decreased after each HD session. ALT was also detected in 18% and 23% of the patients with gout and RA, respectively. ALT was found to be generated by ultraviolet radiation or by the addition of H2O2 to a normal pool-plasma. Addition of Fe(2+) and H2O2 increased the ALT level to about twice that of only H2O2. Addition of either catalase, desferal, EDTA, DMTU, DMSO or mannitol to the plasma decreased ALT generation. These findings suggest that ALT is generated from UA attacked by free radicals, especially by the hydroxyl radical, and that UA plays a role as an antioxidant in the plasma of patients with CRF and some other diseases.