AbstractSpontaneous and chemically induced mutation was examined in the lamba light chain immunoglobulin gene in a human B‐lymphoblastoid cell strain (T5‐1). The hemizygous lambda gene is a unique mutational target gene which codes for a protein that is both expressed on the cell membrane and secreted. Mutations in the lambda gene were detected by analysis of western blots of isoelectric focusing gel electrophoresis of T5‐1 cell conditioned culture medium. None of 5,841 individual clones established from vehicle‐exposed populations had detectable variations in the isoelectric banding pattern of the constitutively secreted lambda immunoglobulin protein. In contrast, 113 of 6,128 clonal populations established from N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG)‐exposed populations exhibited stable variations in expression of the lambda immunoglobulin: isoelectric variants (n = 3) and nonsecretors (n = 110). MNNG‐induced mutations in the lambda gene, which resulted in lambda immunoglobulin proteins with altered isoelectric points (pIs), occurred at a frequency of no less than 4.9 × 10−4mutations/cell, indicating the mature rearranged lambda immunoglobulin gene is comparably sensitive to carcinogen induced mutation as other human autosomal target genes. Approximately one‐half of the MNNG‐induced non‐secretor mutant clones lacked lambda mRNA while one‐half maintained constitutive transcription and expression of the lambda immunoglobulin on the cell surface, demonstrating that carcinogen damage interdicted gene function at multi