When peripheral blood lymphocytes (PBL) were stimulated in vitro with the rough form of type 2Streptococcus pneumoniaeR36a, the resulting plaque‐forming cells (PFC) did not produce antibodies directed against phosphorylcholine, a major antigenic determinant of the cell wall C‐polysaccharide. Instead, R36a stimulated polyclonal PFC in PBL and splenic lymphocytes. We compared the polyclonal responses stimulated by R36a with those induced by two well‐characterized polyclonal activators (PA),Staphylococcus aureusCowan I and pokeweed mitogen (PWM). We found that R36 a was a poor mitogen for PBL, whereas the other two PA were potent mitogens; that the predominant isotype produced in response to all three PA was IgM; that adherent cells strongly inhibited the polyclonal PFC response to both R36a andStaph. aureusbut not PWM; and that T cells were necessary for induction of polyclonal antibody‐secreting cells by all three