Homocysteine (Hcy), an intermediary sulfur AA, is recognized as a powerful prooxidant with deleterious effects on physiological and immune functions. In piglets, there is an acute 10-fold increase of plasma concentrations of homocysteine (pHcy) during the first 2 wk of life. This project aimed to maximize pHcy variations within physiological ranges using typical supplies of folates and vitamin B-12 (B-12) to sows and piglets. Growth, immune response, and Hcy metabolism of piglets were studied until piglets reached 56 d of age. Third-parity sows were randomly assigned to a 2 x 2 split-plot design with 2 dietary treatments during gestation and lactation, S- (1 mg/kg folates and 20 mu g/kg B-12, n = 15) and S+ (10-fold S- levels, n = 16), and 2 treatments to piglets within each half litter, intramuscular injections (150 mu g) of B-12 (P+) at d 1 and 21 (weaning) and saline (P-). Within each litter of 12 piglets, 3 P+ and 3 P- piglets were studied for growth and Hcy metabolism, and the others were studied for immune responses. During lactation, plasma B-12 decreased and was transiently greater in S+ vs. Spiglets on d 1 and P+ vs. P-piglets on d 7 (sow treatment x age and piglet treatment x age; P < 0.05). From 14 to 21 d of age, pHcy was 33% lower in S+ P+ vs. S- P- piglets (sow treatment x piglet treatment interac-tion; P < 0.05). At 56 d of age, hepatic B-12 was greater and pHcy was lower for P+ vs. P-piglets (P < 0.05). No treatment effect was observed on growth except for a lower postweaning G: F in S+ P- piglets than in others (sow treatment x piglet treatment interaction; P < 0.05). Positive correlations were observed between pHcy and growth (r > 0.29, P < 0.05) before and after weaning. Antibody responses to ovalbumin and serum tumor necrosis factor-a were not affected by treatments, but postweaning serum IL-8 peaked earlier in S- P- vs. S+ P+ piglets (piglet treatment x age; sow treatment x piglet treatment interaction, P < 0.05). Proliferation of lymphocytes in response to the mitogen concanavalin A tended to be lower in culture media supplemented with sera from S- vs. S+ piglets (P = 0.081) and P- vs. P+ piglets (P = 0.098), and the reduction of response was more marked (P < 0.05) with high (> 21 mu M) compared to medium (17 to 21 mu M) or low (< 17 mu M) pHcy. In conclusion, the present vitamin supplements to sows and/or piglets produced variations of pHcy that were not apparently harmful for growth performance of piglets. The greater pHcy, particularly prevalent in S- and/or P- piglets, had negative effects on some indicators of immune responses, suggesting that these young animals may be immunologically more fragile.