Expansion of trinucleotide repeats within genes is well known to cause pathological conditions in humans. Here we report a large number of genes containing simple sequence repeats (SSR) from the brain of channel catfish, of which a homologue of the RAD23B gene was found to include (CCA) trinucleotide repeats within its coding region. Because of the importance of the RAD23B gene in the nucleotide excision repair (NER) system, the catfish RAD23B locus was further characterized. The (ACC) repeats encode a polythreonine (T) tract within the catfish RAD23B gene that is absent from the previously cloned human and mouse genes. A survey of the allele variation at the locus indicated the existence of variable microsatellite repeats in the NER RAD23B gene, suggesting that the trinucleotide repeats are expanding or shrinking. The majority of individuals harbor 10 (ACC) repeats within the RAD23B gene, but alleles with 8 and 11 repeats were also detected. The (ACC) repeats are limited to only channel catfish and the closely related blue catfish, but are absent from flathead catfish and the cloned human and mouse genes, suggesting that the microsatellite invasion into the RAD23B gene is a recent event in evolution.