Three levels of variation are described in the response to sheep red blood cells (SRBC). Inbred strains of mice are distinguishable in terms of early or late kinetics of IgM response, high or low overall IgG response, and the relative expression of IgG1, IgG2a and IgG2b antibody in their response to SRBC. Results using C57BL/10 hybrid progeny strongly suggest a genetic control of these different aspects of the anti-SRBC response. The IgM kinetic pattern and the quantitative IgG response are regulated by two independent multigenic systems. Evidence is also presented for a distinction between the genes controlling the quantitative IgG response and those which control the 7 S isotypic pattern. IgG2a antibody expression seems regulated by a single gene. Neither group of genes involved in these various types of regulation seems directly linked to the H-2 complex or to the CH allotype. The hypothesis that 4 different sets of genes might control IgM, IgG1, IgG2a and IgG2b expression is discussed.