The ability of monoclonal mouse IgM, IgD and IgG anti‐(4‐hydroxy‐3‐nitrophenyl) acetyl (NP) antibodies to activate mouse complement was studied using a hemolytic assay. Efficient hemolysis was obtained with IgG_2a, IgG_2b and IgG₃ antibodies but no lysis was observed using a monoclonal IgD. Of several IgG₁ antibodies tested, three gave no detectable hemolysis, although weak but significant hemoloysis was obtained with two other IgG₁. IgM was found to be powerfully hemolytic in that it was effective at lower concentrations than were IgG. However, using complement from mouse strains carrying the H‐2^k haplotype it was found that, under conditions of complement limitation and saturating antibody, a fixed amount of complement could lyse about 3 to 4 times as many IgG‐coated sheep red cells as IgM‐coated red cells. This discrimination between IgM and IgG as regards the efficiency of complement utilization is controlled by a gene in the S region of H‐2 and is not apparent with complement from mice carrying the b, d or s allele at that locus.