A variety of cytotoxic alloantisera directed against murine cell surface components were analyzed for their content of specific IgG1, IgG2a, and IgG2b antibodies by radioimmunoassay, and specific IgM antibodies by 2-mercaptoethanol inhibition of cytotoxicity. Results indicate: (1) that the IgM and IgG subclass content of specific antibodies in anti-Lyt antisera produced at M.I.T. and Sloan-Kettering using the same donor and recipient strains are similar; (2) that specific antibodies produced concurrently in the same mice against at least two different alloantigens (Lyt-3.1 and H-2k) can differ in IgG subclass content; and (3) that preparation of alloantisera against a given antigen (Lyt-3.1) using different combinations of donor and recipient strains can yield specific antibodies which differ in IgG subclass and cytotoxic IgM content. Thus, it appears that humoral immune responses to cell surface alloantigens are not random, but reflect both the antigens being recognized and the strains employed for the immunization. © 1979 Springer-Verlag New York Inc.