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Dr. Takako Yokozawa, Department of Applied Biochemistry, Research Institute for Wakan-Yaku, Toyama Medical and Pharmaceutical University, Sugitani, Toyama 930-01 (Japan) Dear Sir, Methylguanidine (MG) is a probable uremic toxin demonstrated to have a strong association with the induction of uremia. The idea that creatinine (Cr) is a precursor of MG is currently dominant. Giovannetti et al. [1], Perez and Faluotico [2], Gonella et al. [3], Orita et al. [4] and Nagase et al. [5] have reported a positive correlation between the blood Cr level and the degree of MG production, indicating that Cr is very probably a precursor of MG. Our previous study using normal rats and rats with renal failure also demonstrated that MG production increased in proportion to an increase in the level of Cr in the blood [6]. We also examined temporal changes in MG production after Cr loading, and found that the MG produced was excreted rapidly into the urine in normal rats [6]. On the other hand, the production of MG from Cr seems to be increased by factors which promote MG synthesis and inhibit MG degradation. Recently, Aoyagi et al. [7] observed an increased in vitro production of MG from Cr in the presence of active oxygen. Furthermore, in an experiment using isolated rat hepatocytes, they also demonstrated the inhibition of MG production by dimethyl sulfoxide (DMSO), a scavenger of hydroxyl radical, suggesting the involvement of active oxygen in MG production [7]. Data indicating histological damage due to active oxygen in patients with renal failure have been reported by Fillit et al. [8], Giardini et al. [9], Kuroda et al. [10] and Flament et al. [11]. On the basis of these reports, it is considered that, in a state of renal failure, active oxygen increases in quantity and reacts with Cr, resulting in enhanced MG production. However, it remains unclear to what extent active oxygen contributes to the in vivo production of MG from Cr. In this connection, the involvement of hydroxyl radical was investigated using radical scavengers under conditions of increased MG production after Cr loading. Table 1. Effect of hydroxyl radical scavengers on MG production from Cr Scavenger Dose MG μg/3h DMTU 0 13.07 ± 0.80 mg/kgB.W. 20 8.47 + 0.29* 100 6.86 ± 0.28* 500 6.34 ± 0.40* DMSO 0 13.81 ± 0.92