Cellular retinoic acid binding proteins (CRABP) are low molecular weight proteins whose precise function remains unknown. To investigate the role of CRABP in human skin we have cloned the human CRABP-II cDNA as well as the coding region of human CRABP-I. The predicted amino acid sequences of human CRABP-I and CRABP-II demonstrated a 99.3 and 93.5% identity to mouse CRABP-I and CRABP-II, respectively. CRABP-I transcripts were undetectable in adult human epidermis by RNA blot hybridization, while the CRABP-II cDNA probe detected an approximately 1.2-kilobase mRNA transcript. External application of 0.1% retinoic acid cream in vivo for 16 h resulted in a 16-fold induction of CRABP-II transcripts, while CRABP-I mRNA remained undetectable. Expression of CRABP-II, but not CRABP-I mRNA, was also markedly increased (greater than 15-fold) by retinoic acid treatment of fibroblasts cultured from human skin, whereas no significant induction of CRABP-II mRNA was observed in human lung fibroblasts. Human CRABP-II but not CRABP-I mRNA was significantly increased by agents which are known to induce keratinocyte differentiation in vitro. The marked inducibility of the CRABP-II gene is compatible with the idea that this isoform is important in retinoic acid-mediated regulation of human skin growth and differentiation.