The effect of exposure to uncontrollable shock on the production of antibodies to a novel antigen, keyhole limpet hemocyanin (KLH), was studied in adult male Sprague-Dawley rats. Groups of rats were tested under one of four experimental conditions which included testing during either the light or dark portions of their light cycles and following either one or three daily exposures to tail shock. Control subjects were immunized with KLH in the absence of shock exposure during either the light or dark phases of their light cycle. A tertiary (memory) response was evoked 60 days following the initial immunization sequence in all animals in the absence of a shock exposure. Blood samples were obtained from the tip of the tail at the time of each immunization and at 1-week intervals for 3 weeks following immunizations. Specific IgG antibodies to KLH were determined by an enzyme-linked immunosorbent assay (ELISA). All animals exposed to shock showed reduced levels of IgG antibodies to KLH regardless of the experimental conditions of shock exposure. Antibody levels were highest among animals immunized during the dark phase of their cycle for both control and shocked animals. Antibody production to a novel antigen appears to be a robust and sensitive measure for studies of modulation of immunity by behavioral factors.