Non-T cells from tonsil or blood were fractionated according to buoyant density, isotype of surface immunoglobulin, or the ability to form rosettes with mouse erythrocytes. Each fraction was tested for the ability to proliferate in response to B. catarrhalis (Bc) and, for comparison, Staphylococcus aureus Cowan 1 (SAC) or an MLR supernatant (TF). Cells in all density fractions responded to Bc, the greatest response occurring in the high-density cell fraction. SAC could similarly induce proliferation in high-density cells, in contrast to TF which preferentially activated cells in the low-density fraction. When cells were fractionated by rosetting with mouse erythrocytes, both fractions (MRBC-R+ and MRBC-R-) responded to Bc and to SAC, whereas the greatest response to TF occurred in the MRBC-R- cell fraction. Depletion of sIgD+ sIgM+ cells almost completely abolished the response to Bc, suggesting that responsive cells express both these classes of immunoglobulin on their membrane. Furthermore inclusion of anti-delta antibodies in cultures resulted in failure to proliferate in response to Bc. These data strongly suggest that Bc, like SAC but in contrast to TF, is able to stimulate proliferation in cells with the characteristics of resting B cells, i.e., high-density, sIgD+ cells which form rosettes with MRBC. This may be related to the fact that Bc, like SAC, is able to bind to human immunoglobulins.