B cell antigen receptor (BCR) ligation leads to receptor desensitization wherein BCR remain competent to bind antigen and yet fail to transduce signals. Desensitized BCR exhibit a defect at the most proximal level of signal transduction, consistent with failed transmission of signals through the receptor complex. We report that antigen stimulation leads to dissociation or destabilization of the BCR reflected by inability to coimmunoprecipitate Ig-α/Ig-β with mIg. This destabilization is temporally correlated with desensitization and occurs in BCR containing mIgM and mIgD. Induction of BCR destabilization requires tyrosine kinase activation but is not induced by phosphatase inhibitors. BCR destabilization occurs at the cell surface and "dissociated" Ig-α/Ig-β complexes remain responsive to anti-Ig-β stimulation, suggesting that mIg-transducer uncoupling may mediate receptor desensitization.