Aldose reductase (AR), the first enzyme in the polyol pathway, has been implicated in the pathogenesis of diabetic complications, although its physiological role is unclear. In mice, besides AR, two AR-like proteins, mouse vas deferens protein (MVDP) and fibroblast growth factor-regulated protein (FR-1), have been reported recently. Tissue-specific expression of these two genes was examined using the RNase protection assay method. Contrary to previous reports, MVDP was detected in a variety of tissues besides the vas deferens. High levels of MVDP mRNA were found in the adrenal glands, and low levels of expression were detected in eye, intestine, seminal vesicle, kidney, liver, testis and lung. The major gene expression pattern for FR-1 was slightly different from that of MVDP, with the highest levels of mRNA detected in testis, heart, adrenal gland, and ovary; less was found in the lung and it was barely detectable in eye, intestine, liver and seminal vesicle tissue. Mouse embryos, as early as 10.5 days post coitum, expressed both genes, although the levels of expression were different. Human AR mRNA was found in human vas deferens, although not at the high level found in mice. The localization of both MVDP and FR-1 transcripts in the adrenal cortex by in situ hybridization led to the speculation that these two AR-like proteins could be related to hormone production.