AbstractMutants of a hybridoma line secreting IgM with anti‐trinitrophenyl specificity were enriched by coupling the hapten to the cell surface and incubating the cells in the presence of complement. In this way, cells secreting wild‐type Ig commit suicide, whereas cells secreting IgM with reduced lytic activity preferentially survive. Mutants have been isolated which showed no or reduced synthesis of either the heavy or the light chain of the IgM molecule, mutants with internal and carboxy‐terminal deletions of the μ chain, and a mutant with an electrophoretically silent change of the μ chain that reduces the affinity of the antibody for the hapten tenfold. The frequency of mutants in the original population was estimated to be about 10−4 to 10−5. All mutants were stable with reversion frequencies of about 10−5 or less.