The nonimmune adult spleen contains at least two B-cell subpopulations. The majority of primary B cells express cell surface Ia determinants and have the capacity to give rise to IgG antibody-producing clones after T-cell dependent antigenic stimulation. There is also a small subpopulation of primary B cells which are, by definition, Ia negative, since their activity is not eliminated by negative selection with anti-Ia serum and complement. The Ia-negative B cells give rise to clones that produce only IgM antibody. These B-cell subsets may form a continuum in B-cell maturation, or they may exist as discrete B-cell lineages. Since the cellular expression of Ia antigens appears to correlate with the ability of the B cell to generate IgG-producing clones, it is speculated that Ia molecules may have a role in the IgM to IgG B-cell switch mechanism.