Significant immunoglobulin (Ig) production by human peripheral blood lymphocytes was induced in vitro by stimulating the cells with pokeweed mitogen (PWM) and Staphylococcus aureus Cowan I (SpA Col). IgG, IgM, and IgA were determined by a combination of the latex fixation test and radioimmunoassay. High levels (1,000 to 5,000 pg/ml) of IgG and IgM and a lesser amount of IgA were constantly produced during 7 to 8 days of incubation with both stimulants. Ig production induced by SpA Col stimulation was independent of the presence of T cells, while Ig production induced by PWM required T cells exclusively. Depletion of monocytes in the culture caused but a slight decrease in Ig production (particularly in the case of IgG). While the addition of a small number of monocytes enhanced IgG induction by both stimulants, coculture with an excess number of monocytes inhibited Ig induction (particularly IgG) by PWM stimulation but not by SpA Col stimulation. Marked suppression of Ig production (IgG, IgM, and IgA) was observed in cocultures with Con A-activated T cells. The phenomena of suppression were observed in both the SpA Col-stimulated and PWM-stimulated lymphocytes. These data indicate that Ig production from B cells stimulated with a polyclonal B cell activator, SpA Col, was independent of T cells and relatively of independent of monocytes, but could be subjected to the regulation of the Con A-induced suppressor T cells.Polyclonal B cell activators have been invaluable tools in immunobiology, since the use of these stimulants has provided useful information about various aspects of B cell differentiation and its function. Few substances which can selectively activate human B cells are known except for killed Staphylococcus aureus bacteria (SpA Col) (9,15,28), Nocardia water soluble mitogen (4, 18), and Epstein-Barr (EB)-virus (3). SpA Col is a potent B cell mitogen which stimulates B cells directly through different pathways from those of pokeweed mitogen (PWM), since SpA Col does not require the presence of T cells whereas PWM-induced activation is absolutely T cell dependent.Only limited evidence for polyclonal activation with SpA Col has been found, 1345