Mononuclear cells (MNC) isolated from bone marrow curettaged from human ribs spontaneously produced significant amounts of Iga in 14-day in vitro culture. When culture supernatants were tested for each immunoglobulin isotype by radioimmunoassay at days 7, 14, 21, and 28, the peak of spontaneous IgA production was reached by day 14. Culturing marrow MNC in the presence of the polyclonal activator pokeweed mitogen (PWM) ablated this spontaneous IgA activity, and did not stimulate the production of IgG or IgM. In contrast, peripheral blood MNC produced significant amounts of all three immunoglobulin isotypes studied in the presence of PWM, but minimal immunoglobulin spontaneously. PWM stimulated both marrow and peripheral blood MNC to proliferate as demonstrated by increased DNA synthesis. In view of the opposite effects of PWM on immunoglobulin production by peripheral blood and bone marrow MNC, PWM may be stimulating a different functional or developmental subpopulation of cells in each case. We conclude that the bone marrow is a major site of IgA production in the human, that cells within the bone marrow have a blastogenic response to PWM in vitro, and that spontaneous production of IgA by human marrow MNC is inhibited by PWM.