The physiology of the epididymis is an integral part of the maturation process by which human spermatozoa acquire the ability to reach and fertilize an oocyte. Because of the high degree of species specificity exhibited by the epididymal proteins involved in sperm maturation, we have assessed tissue from several alternative species for their suitability as a model for human epididymal physiology. Of these, the dog appears to offer an appropriate system. Northern hybridization using cDNA probes specific for human epididymal genes established that, irrespective of dog breed, the canine equivalents of the epididymis-specific HE1, HE4 and HE5 mRNAs were expressed highly in the canine epididymis. cDNA cloning and sequencing confirmed that the canine gene products, CE1, CE4 and CE5 were indeed true structural homologues of their human counterparts. Finally, tissue culture conditions were established wherein all three specific canine genes remained up-regulated after 5 days of culture. Thus, the prerequisite criteria for the development of a system which models human epididymal physiology are to a large degree fulfilled by this canine culture system.