Five healthy males, age 25-32 y, were fed in sequence a diet of ordinary foods (10 d, PI), a low-methionine diet (285 mg/d, 14 d, PII), and an adequate-methionine diet (725 mg/d, 7 d, PIII). Diets contained 9 g nitrogen (N) per day with soy protein and synthetic L-amino acids as the N sources in PII and PIII. In PII, subjects were in negative N balance whereas, in PIII, four subjects were in positive N balance. On the last day of each period, fasting subjects ingested a dose of nicotinamide (NAM, 102 mumol/kg body wt). Plasma and urine samples were analyzed for methylated derivatives of NAM by high-performance liquid chromatography (HPLC) methods. Mean values of methylated metabolites in urine from the three diet periods (for four subjects in N balance during PIII) were not different (59.8, 56.7, and 59.9 mumol/(kg body wt X 24 h) for PI, PII, and PIII, respectively). Plasma values of these metabolites also were similar. Results suggest that during a 2-wk period of negative N balance due to a low-methionine intake hepatic methylation processes are not impaired. These processes appear to have a higher metabolic priority than maintenance of the net protein synthesis rate.