The molecular basis of a human immunoglobulin deficiency characterized by the complete absence of κ chains has been investigated by nucleotide sequence analyses of a patient's κ constant region (C κ ) genes. Both of his C κ genes had a single point mutation, resulting in the loss of the invariant tryptophan from one allele and of an invariant cysteine from the other allele. These results indicate that neither of the patient's C κ alleles encoded a κ chain that could form a stable intradomain disulfide bond, although peculiarities in the expression of κ chains in the patient's family suggest that other factors may be involved.