Rat spleen cells were stimulated with pokeweed mitogen (PWM) and the IgM and IgE responses were assessed. An enrichment of the cell suspension with IgE-bearing cells before stimulation resulted in an increase in the number of IgE-secreting cells. A decrease of the number of IgE-secreting cells was found after depletion of IgE- or IgM-bearing cells, but not those bearing IgD molecules on their membranes, before stimulation. Moreover, the stimulation of membrane IgE on B cells with anti-IgE antibodies was shown to increase the number of IgE-secreting cells after PWM-induced differentiation in vitro. In vivo, it was also observed that a single injection of anti-IgE antibodies can induce the differentiation of IgE-secreting cells. These results demonstrate the presence of IgE(+)-IgM (+)-IgD- B cells in the rat that are responsive to PWM-induced differentiation into IgE-secreting cells. They indicate a pre-commitment of these cells at a stage where they still express IgM on their surface. IgE molecules on the cell membranes play a role in their differentiation.