Regulation of immunoglobulin-secreting cells (ISC) was studied in human IgG B-cell line ARH-77, as assayed by reverse plaque formation. Numbers of ISC were stimulated by both lymphokine (stimulation index = 1.5-8.7) and phorbol myristic acetate (PMA) (stimulation index = 2.7-42). Incubation of ARH-77 with the two agents together caused additive or superadditive numbers of ISC, suggesting that they acted on this B cell via different mechanisms. B-cell-inducing factors stimulating IgG ISC in ARH-77 line were found at 20,000 and 40-60,000 molecular mass. The 20-KDa factor could be distinguished from IL-2 by affinity chromatography on blue agarose. Stimulated cells maintained their immunoglobulin class, and no evidence for isotype switching to IgM or IgA was detected using lymphokine or PMA. The cell line is a model for normal B lymphocytes which have been activated, for example, by Staphylococcus bacteria, to respond to T-cell factors.