Most mature B lymphocytes co-express two classes of antigen receptor, IgM and IgD. The differences in the signal transduction from the 2 receptors are still a matter of controversy. We have analysed B-cell lines expressing IgM or IgD antigen receptors with the same antigen specificity. Cross-linking of these receptors with either antigen or class-specific antibodies results in the activation of protein tyrosine kinases and the phosphorylation of the same substrate proteins. The kinetics and intensity of phosphorylation, however, were quite different between the 2 receptors when they were cross-linked by antigen. In membrane IgM-expressing cells, the substrate phosphorylation reached a maximum already after 1 min and diminished after 60 min whereas in the membrane IgD-expressing cells, the substrate phosphorylation increases further over time, reached its maximum at 60 min and persisted longer than 240 min after exposure to antigen. Recently prolonged signaling has been found to be responsible for signaling differences between tyrosine kinase receptors using otherwise similar signaling routes. Thus, the duration of a signal may be an important biological feature of signal transducing cascades.