After its original description as a steroid-dependent protein in the rabbit uterus, uteroglobin became one of the best characterized proteins. However, detailed knowledge of its physiological role remains an enigma. In this study we investigate how its structure is phylogenetically conserved in the horse compared to other mammalian species. Northern blot analysis showed that in horses, the main expression of uteroglobin appears in lung, uterus, and prostate tissues. Western blot analysis demonstrated that the dimeric form of uteroglobin is found predominantly in biological compartments. Using a RACE-PCR technique, we cloned and sequenced the full-length cDNA (473 base pairs) that encodes equine uteroglobin. The nucleotide sequence was shown to characterize the primary structure of this protein. This enabled us to add equine uteroglobin to a comparative amino acid alignment of 8 other uteroglobin molecules, and finally, to unravel 14 evolutionary completely conserved amino acids. We summarize these results with a computer-based 3-D model of horse uteroglobin, and discuss new concepts on the physiological role of uteroglobin, in particular as a specific binding protein.