Peripheral blood lymphocytes from patients with antibody deficiency diseases (primarily agammaglobulinemia) were examined for the presence of B-lymphocyte subsets defined by surface immonoglobulin isotypes. The patients could be classified into one of four groups based upon the presence or absence of particular isotype-defined subsets. Patients with type I agammaglobulinemia lacked cells bearing surface IgG as well as IgD-Igm+-bearing cells. Type II agammaglobulinemia had unusually large numbers of IgG-bearing cells, representing as many as 50% of the peripheral blood B lymphocytes, while other B-cell subsets were present in normal numbers. Type III agammaglobulinemia had apparently normal numbers of all B-cell subsets. Hyper IgM immunodeficiency lacked cells bearing surface IgG, but did have all three iGd/IgM-bearing B-cell subsets. This classification of patients based upon B-cell subsets present in peripheral blood directly correlates with previous functional studies of B cells from these patients. We suggest that abnormal in vitro function of cells from these patients results from abnormal populations of B cells in peripheral blood, which result from the underlying disease.