The uptake of tritiated thymidine by isolated peripheral blood lymphocytes obtained from male guinea pigs immunized with bovine serum albumin was studied in animals maintained on various amounts of Vitamin C for 28 days. Animals were pair-fed on ascorbate-free diet and were supplemented intraperitoneally with 0, 25, or 250 mg Na-ascorbate per day. Scorbutic animals lost weight rapidly during the final 2 experimental weeks. Their daily food intake averaged only 4 g/day during the last week; thus, pair-fed ascorbate-supplemented groups were also subjected to acute nutritional stress. Lymphocytes from guinea pigs receiving 250 mg Na-ascorbate per day incorporated in vitro the highest amounts of tritiated thymidine both in the absence of nonspecific mitogen and in the presence of concanavalin A or phytohemagglutinin. Responses to lipopolysaccharide were not conclusive. Total circulating white cells counts and relative numbers of T and B lymphocytes were assessed in a second study made under identical constraints. In scorbutic animals the percentage of B lymphocytes increased and that of T lymphocytes decreased continuously over the 4-week period. The opposite effect was observed in vitamin C-supplemented animals. These studies suggest that very high doses of ascorbate support elevated mitotic activity after 4 weeks of much reduced food intake.