The effects of the injection of a large amount of N1-methylnicotinamide (MNA) (500 mg per kg body weight) on the ratio of N1-methyM-pyridone-S-carboxamide (4-py) to N1-methyl-2-pyridone-5-carboxamide (2-py) excretion, and the activities of 2-py and 4-py forming MNA oxidases were investigated in rats. The injected MNA was excreted very rapidly into the urine; 46% of the dose was excreted from 0-3hr post-injection, 15% from 3-6hr, 6% from 6-9hr and 1.5% from 9-12hr. The ratio of 4-py to 2-py also decreased rapidly; the ratio being about 0.6, 0.4, 0.4 and 0.6 from 0-3hr, 3-6hr, 6-9hr and 9-12hr post-injection, respectively. This ratio then recovered rapidly; being about 2, 5.5, 8.5 and 9.7 from 12-24hr, 24-48hr, 48-72hr and 72-96hr post-injection, respectively. The normal range of 4-py to 2-py excretion ratio is 8-14. So, this ratio returned to a normal level by day 3 post-injection. The rats were killed 5 hr after the MNA injection. At this time (the lowest ratio was observed around this time), the activities of 2-py and 4-py forming MNA oxidases in the injected group were 59% and 11% of the normal levels, respectively. Therefore, it was found that the decreased ratio of 4-py to 2-py excretion with the MNA injection was mainly due to the higher inhibition of the 4-py forming MNA oxidase than of the 2-py forming MNA oxidase by the MNA injection.