The onset of lactation in dairy cows is characterized by high output of methylated compounds in milk when sources of methyl group are in short supply. Methionine (MET) and choline (CHOL) are key methyl donors and their availability during this time may be limiting for milk production, hepatic lipid metabolism, and immune function. Supplementing rumenprotected MET and CHOL may improve overall performance and health of transition cows. observed in response to CHOL supplementation, expression of (BHMT) and MTR and BHMT enzyme activity did not change (P > 0.05). Furthermore, overall MTR enzyme activity was lower (23.5 vs. 29.6 nmol product h -1 mg protein -1 ; SEM = 2.9; P = 0.05) in CHOL cows. In terms of AA profile, MET supplementation led to greater (P < 0.01) circulating methionine and proportion of methionine in the essential AA pool, total AA, and total sulfur-containing compounds. Lysine in total AA also tends to be greater (P = 0.08) in these cows, indicating a better overall AA profile. Sulfur-containing compounds (cystathionine, cystine, homocystine, and taurine) also were greater (P < 0.05) in MET-supplemented cows, indicating an enriched sulfur-containing compound pool due to enhanced transsulfuration activity. Circulating essential AA (P = 0.06) and total AA (P = 0.03) concentrations were greater in MET cows due to greater lysine, arginine, tryptophan, threonine, proline, asparagine, alanine, and citrulline. In contrast, tryptophan and cystine were greater. Plasma 3-methylhistidine concentration was lower (P = iv 0.02) in response to CHOL, suggesting less tissue protein mobilization in these cows. Overall, results indicate that MET supplementation improves performance of transition cows through a combination of better immunometabolic status, plasma AA profile, and a reduction in oxidative stress; insufficient regeneration of MET may be one reason for the lack of effect with supplemental CHOL.