The alleviation mechanism of methionine toxicity by dietary glycine was investigated in weanling rats fed a high-methionine diet. When rats were fed a 10% casein diet containing 2% methionine, the activities of methionine adenosyltransferase, cystathionine beta-synthase, and cystathionine gamma-lyase, which participate in the methionine metabolism in the transsulfuration pathway, were significantly enhanced. But the addition of 2% glycine to the high methionine diet did not cause further increase in these enzyme activities; the activities of methionine adenosyltransferase and cystathionine beta-synthase were rather decreased while cystathionine gamma-lyase activity was not altered. Methionine transaminase activity was essentially insensitive to the dietary addition of methionine and glycine. In rats fed a high methionine diet, the hepatic methionine level was significantly increased with a concomitant decrease in the levels of glycine, serine, and threonine. The addition of glycine to the high methionine diet effectively suppressed the enhancement of the hepatic methionine level and almost completely restored the glycine level, but it only partially restored the serine level and further decreased the threonine level. From these results, it is suggested that the alleviating effect of dietary glycine on methionine toxicity is primarily elicited by the restoration of the hepatic glycine level rather than by an increase in hepatic enzyme activity.