This report describes the activity of recombinant human Rdh5 (11-cis-retinol dehydrogenase) with steroids and retinoids and expression of the Rdh5 mRNA in extra-ocular human tissue. The data show that Rdh5 catalyses 9-cis-retinol metabolism equally efficiently as 11-cis-retinol metabolism and recognizes 5alpha-androstan-3alpha,17beta-diol and androsterone as substrates (3alpha-hydroxysteroid dehydrogenase activity), but not testosterone, dihydrotestosterone, oestradiol and corticosterone (lack of 17beta-hydroxysteroid and 11beta-hydroxysteroid dehydrogenase activities). Rdh5 mRNA expression was widespread in extra-ocular tissues with human liver (100% relative expression in extra-ocular tissues only) and mammary gland (97% relative to liver) showing the most intense signals. Other noteworthy relatively intense expression sites included colon (45%), thymus (43%), small intestine (39%), kidney (37%), bladder (29%), pancreas and spleen (28% each), heart (26%), uterus and ovary (25% each), testis (22%) and spinal cord (24%). Human fetal tissues also expressed Rdh5 with fetal liver showing the most intense expression among the fetal tissues (20%). Considered along with the identical nucleotide sequences in the untranslated regions of human Rdh5 and human 9-cis-retinol dehydrogenase cDNAs and the nearly identical nucleotide sequences overall (99% identity), the current results suggest that the two cDNAs represent a single gene product.