A Saccharomyces cerevisiae homolog to Drosophila melanogaster and mouse Tcp-1 encoding taiDless complex polypeptide 1 (TCP1) has been identified, sequenced, and mapped. The mouse t complex and many of its unusual properties have attracted the attention of geneticists for nearly 60 years (11,12,20,60). t alleles were first discovered by their interaction with a dominant T-locus mutation to produce a tailless phenotype in double heterozygous T/t animals. Heterozygous T/+ animals have a short tail, and homozygous T/T animals are embryonic lethals. Homozygous tx/tY males are sterile (37, 38), and heterozygous +/t animals have tails of normal length and are visually indistinguishable from normal wild-type +/+ animals. Compared with wild-type laboratory chromosome 17, the principal variation in t chromosomes consists of at least four inversions of about 1% of the mouse genome (30 Mbs of DNA) (21, 23). The t complex is the name given to the rearranged region. It contains about 100 genes (39), including several genes expressed in the testes whose products show t-allele-specific alterations.t chromosomes confer a number of effects, including disturbances of embryonic development, alterations of sperm differentiation and function, and transmission ratio distortion. While transmission of the t complex through females is normal, heterozygous t/+ males transmit the t-bearing chromosome to their progeny in excess of the Mendelian expectation. Genetic analysis of transmission ratio distortion suggests that it depends on the action of up to four distorter loci (Tcd-J to Tcd4) as well as a responder locus (Tcr) (2, 36-38, 56, 63). The molecular basis of transmission ratio distortion remains unknown.A number of candidate genes for the distorter and responder loci, including Tcp-1, have been isolated from the t complex (75). Tailless complex polypeptide 1 (TCP-1), a protein of 57 kDa, is expressed in large amounts during * Corresponding author.