Methyl groups, via the diet or folate-dependent one-carbon pool, are utilized in S-adenosylmethionine-dependent transmethylation reactions to produce important biological compounds. Glycine N-methyltransferase (GNMT) is an important protein in regulating the metabolism of methyl groups. GNMT has been shown to be induced by all-trans-retinoic acid (RA) and is subject to inhibition by 5-methyltetrahydrofolate. The three studies presented in this thesis examine factors that impact methyl group metabolism, including vitamin A and folate status, age, and gender. The objective of the first study was to compare the effects of a less toxic retinoic acid derivative, retinoyl β-glucuronide (RAG), and RA on GNMT activity in vitamin A sufficient (VAS) and vitamin A deficient (VAD) rats. RA increased GNMT activity [difference]230% in VAS and VAD rats, while RAG increased GNMT activity in VAS rats only (107%). This study indicates that RAG is less effective than RA at modulating GNMT activity, regardless of vitamin A status. In the second study we examined the effects of age and gender on methyl group metabolism in RA-treated rats. GNMT activity was increased in both 4- and 10-wk old male RA-treated rats (213% and 647%, respectively), and in 10-wk old female rats (229%). Plasma total homocysteine concentration was reduced ([difference]36%) in 10-wk old male RA-treated rats compared to controls. This study demonstrates that male rats are more sensitive than female rats to retinoid-mediated disruptions of methyl group and homocysteine metabolism, and sensitivity increases with age for both sexes. The aim of the third study was to determine how dietary folate levels modulate RA-induced disruption of methyl group metabolism. Rats were fed an amino acid-defined diet containing 0 (deficient), 2 (sufficient), or 8 (supplemented) ppm folate for 5 weeks. Rats were orally administered RA at 0, 5, or 30 [mu]mol/kg BW the last 7 days. Hepatic GNMT activity was significantly increased by RA in all three dietary folate groups; however, this response was attenuated in the 2 and 8 ppm folate groups. These results indicate that moderate folate deficiency results in increased sensitivity to RA-mediated disruption of methyl group metabolism, compared to rats receiving folate.