From an IgM secreting hybridoma line we have isolated 16 spontaneous mutants that produce truncated IgM polypeptides. The size of the mu-mRNAs produced by these mutants is normal, but they express 3- to 100-fold less mu-mRNA and mutant mu-protein than the parental cell line. Nucleotide sequence analysis of cloned mu-genes and/or their mRNAs show frameshift mutations that generate in-phase chain termination codons. The extent of the reduction in mu-mRNA levels depends on the position of the nonsense codon within the gene.