Production of antibodies to pneumococcal polysaccharide from Streptococcus pneumoniae, type III was determined in young rats at different ages and stages of vitamin A deficiency. At 30, 35 and 45 d of age, serum retinol concentrations of vitamin A-depleted rats were 46, 35 and 9%, respectively, of the serum retinol concentrations of pair-fed controls. Specific antibody production was low at 30 d of age for both vitamin A-depleted rats and control rats. Between 30 and 45 d of age, antibody production increased considerably in normal rats; however, the response of vitamin A-depleted rats was only 22% (P less than or equal to 0.001) that of controls at 35 d of age and 8% that of controls (P less than or equal to 0.001) for 45-d-old rats. Lymphocyte populations were examined by flow cytometry. The numbers of immunoglobulin M- and immunoglobulin D-positive cells changed with age, but not as a result of dietary treatment. The numbers of total T cells or helper and suppressor T cell subsets did not differ with age or with vitamin A status. These studies showed that the normal antibody response to pneumococcal polysaccharide develops rapidly after 30 d of age in the rat, that this antibody response is impaired even during the early stages of vitamin A deficiency, and that impaired antibody production does not seem to be accompanied by quantitative differences in splenic lymphocyte populations.