A perfusion technique was utilized to assess the rate of absorption and metabolism of L-methionine by livers isolated from rats fed a diet deficient in zinc. The endogenous concentration of S-adenosyl-L-methionine in the livers from the zinc-deficient rats was near normal, while the concentration in pair-fed controls was approximately 50% of that found in normal livers (ad libitum fed). The rate of uptake of methionine by the livers isolated from zinc-deficient rats was significantly less than in the pair-fed or ad libitum-fed controls. The synthesis of L-methionine, S-adenosyl-L-homocysteine and S-adenosylmethionine was not impaired in the livers from the zinc-deficient rats. However, the methyl group of the S-adenosylmethionine turned over much more slowly in the livers from zinc-deficient rats than in either control group. This was reflected in the depressed rates of methylation of various macromolecules, particularly DNA and histones. The synthesis of nuclear proteins (histones and nonhistone chromosomal proteins) was depressed in the livers from zinc-deficient rats. The reduced synthesis of chromosomal proteins and marked reduction in DNA methylation would be consistent with the finding that DNA biosynthesis and cellular proliferation are markedly depressed in zinc-deficient animals.