Rabbit anti-rat IgD (δ-specific) injected subcutaneously into adult rats resulted in hypergammaglobulinemia, increased serum immunoglobulins, increased antibody production, and alterations in the percentages of PBL expressing IgD and IgM. Serum IgM, IgG2a and IgG2c concentrations were increased 100%, 125%, and 200%, respectively, over controls, whereas IgA levels were not altered. Increases in the serum immunoglobulins were predominately due to an increase in antibodies to the rabbit serum components. A depletion of IgD-IgM bearing lymphocytes in the peripheral blood was observed after 24 hr of injection. Percentages of IgD-IgM bearing lymphocytes returned to normal by day 4 and were significantly increased (∼2-fold) by day 8. The in vivo effects of anti-δ in rats were similar to those reported in the monkey. Possible modes of action of the anti-δ and the significance of these results in relation to the biologic function of membrane IgD are discussed.