Anti-D and anti-c monoclonal antibodies (MABS) were found to be heterogeneous with respect to their activity in five cell-mediated functional assays. The two IgG3 MABS promoted greater rosette formation of red cells with monocytes than the IgG1 MABS. Discrepant results were obtained by different laboratories for the relative effectiveness of the MABS in promoting monocyte-mediated red cell phagocytosis and lysis, which may have been due to variations in the assay methods used. The IgG3 anti-D MAB promoted greater monocyte chemiluminescence than the IgG3 anti-c MAB, but of these two MABs only the anti-c mediated lysis of red cells in lymphocyte ADCC assays. The majority of the IgG1 anti-D MABS were ineffective at promoting red cell lysis by lymphocytes (K cells), but two were active even when diluted 1 in 300. There was no correlation of functional activity with red cell sensitization levels, IgG concentration or D epitope specificity of the MABS.