Much greater increases in S-adenosylmethionine concentrations are observed in the liver in response to methionine-loading than in the brain due to differences in the methionine adenosyltransferase activities in these tissues. Liver methione adenosyltransferase exhibits a bimodal saturation curve with a nonlinear Line-weaver-Burk plot, indicating that high methionine concentrations are required for saturation. In the brain the methionine adenosyltransferase is saturated in vitro at a methionine concentration less than the normal physiological concentration. The increased S-adenosylmethionine concentrations in the livers of methionine-treated rats also account for the observed inhibition of N5,N10-methylenetetrahydrofolate reductase activity in this tissue. No inhibition of this enzyme is observed in the brain of methionine treated animals. Nor are S-adenosylmethionine concentrations increased significantly in brain. Serine hydroxymethyltransferase activity responds to methionine-loading by decreasing in brain and increasing in liver.