The inhibitory effect of various beta-lactams on antibody production in the spleen was evaluated in mice immunized with sheep red blood cells by Cunningham's method. With a few exceptions, cephem derivatives were more effective than the penicillins tested in inhibiting the production of antibodies in the spleen of mice. This tendency was especially marked with cefsulodin, cefmenoxime, cefotiam and ceftazidime. However, no effect was obtained with 6-aminopenicillanic acid or 7-aminocephalosporanic acid. Our findings suggest that the difference among various beta-lactams in inhibitory effect on antibody production resulted from the difference in activities of beta-lactams with different side chains at the 6- or 7-positions.