Cultures of mouse myeloma cells which secrete both heavy (H) and light (L) immunoglobulin chains were cloned in soft agar. Variants that synthesized neither chain, or only light chains, were detected by overlaying the growing colonies with antiserum specific for the individual immunoglobulin chains. The rate of conversion of heavy plus light chain producers to light chain producers was 1.1 x 10(-3) per cell per generation, as determined by fluctuation analysis.