Spontaneous isotype switch variants from IgG1 to IgG2a of monoclonal antibody (MAb) BW 494 were generated. Their frequency was found to be I variant cell out of 2 × 105 parental hybrid cells. The tissue specificity of the parental MAb BW 494 IgG1 was identical to that of the BW 494 IgG2a variant arguing for an unaltered paratope shared by the parent and the variant. In contrast, the switch in isotype from IgG1 to IgG2a resulted in an increase of the variant potential to mediate antibody dependent cellular cytotoxicity (ADCC) reaction with human peripheral blood mononuclear cells as effectors. The potential of variants to perform human complement mediated cytolysis (CDC) was not better than that of the parental MAb.