Vitamin A (VA) deficiency still exists in parts of the developing world where it is associated with increased morbidity and mortality in preschool-aged children. In the present studies, the young rat has been used as a model to investigate the effects of VA deficiency and retinoid repletion on antibody responses to a variety of bacterial antigens. In VA-deficient rats, antibody responses following immunization with capsular polysaccharides or protein antigens were very low, whereas responses to lipopolysaccharides were normal. In all cases of low antibody response, retinol treatment before immunization restored antibody production to control levels. The numbers of B and CD4+ and CD8+ T cells in VA-deficient rats were only modestly reduced, but both natural killer (NK) cell number and NK cell-mediated cytotoxicity were decreased substantially. Even in VA deficiency, antibody responses and NK cell cytotoxicity could be markedly stimulated by certain biological response modifiers.