A 64-year-old woman with a syndrome of thymoma, severe hypogammaglobulinemia, seemingly normal cell-mediated immunity and aplastic anemia, was found to have virtually no immunoglobulin- (Ig) bearing peripheral blood lymphocytes (PBL). However, 7.8 +/- 3.4% of the PBL were positive for another B-cell marker, the receptor for aggregated IgG, while the remaining cells bound sheep erythrocytes. Those cells which were aggregate-reactive appeared to be immature or incomplete B cells. Cultures of peripheral blood leukocytes from the patient in various serum-containing media were studied by 3 independent technics for the development of lymphocyte surface Ig and for Ig in the culture supernatants. In vitro the patient's cells were able to develop surface Ig in media supplemented with fetal calf serum (FCS) or normal serum; in media supplemented with autologous serum, the cells developed no surface Ig. During the cultures in FCS, human Ig determinants became detectable in the medium, and both medium and cell-surface Ig underwent a shift from mu determinants early in the culture period to gamma and alpha determinants later. The development of Ig on the cells was not inhibited by the presence of autologous serum if FCS was included in the medium. These data support the concept that a factor, missing from this patient's serum, is required at an early stage in the maturation of the B cell. A patient with X-linked agammaglobulinemia had a population of circulating lymphocytes with surface characteristics similar to the B cells of the thymoma case. In contrast, no Ig synthesis by this patient's cultured cells could be demonstrated, indicating a different level of block in the 2 cases despite their similarity at the level of the cell surface.