Nocardia water-soluble mitogen (NWSM) is a mitogen which activates human B lymphocytes even in the absence of T cells. Tonsil and peripheral blood lymphocytes cultured in the presence of NWSM gave rise to large numbers of cells containing cytoplasmic immunoglobulins of IgM, IgA or IgG classes. The number of plasma cells appeared to be elevated as early as day 3 of culture and peaked on day 5 or 7. The IgM response preceded the development of cells containing other Ig classes, and was found to remain predominant on days 5 and 7. A similar number of plasma cells were generated in T-deprived suspensions; however, a quantitative regulation by T cells cannot yet be excluded. The response to pokeweed mitogen appeared to be similar, except that it was often less intense and not observed in the absence of T cells. Very few or no IgD-containing cells were found to be differentiated with both mitogens.