Aim: To investigate whether human neural progenitor cells (hNPCs) can be induced to differentiate toward a neuronal phenotype by all-trans Retinoic acid (RA), and whether there is any functional link between p27 Kip1 function and RA in the control of neuronal differentiation in hNPCs. Methods: hNPCs were derived from the striatums of human embryos at 12 weeks' gestation and cultured with serum-free medium in presence of EGF and bFGF. At the appropriate time, hNPCs were exposed to 1 μmol·L -1 RA for 1,3,5, 7days respectively. The properties of hNPCs were characterized by using phase-contrast microscopy, immunocytochemistry and RT-PCR. Results: To monitor morphological changes induced by RA, RA-treated hNPCs were checked by phase-contrast microscopy. After 3 days treatment with RA, the cells began to show phenotypical changes, assuming a neuronal-like morphology with contemporaneous formation of dendritic-like structures. Mature neuronal-like morphology was observed after being exposed to RA for 7 days. By immunocytochemistry, the expression of p27 Kip1 was elevated after exposure to RA for 3 days compared with that of normal untreated hNPCs, and significantly increased after exposure to RA for 7 days (P < 0.05). By RT-PCR, p27 Kip1 mRNA was elevated after exposure to RA for 3 days, with a peak at 5 days. The expression of p21 Cip1 mRNA was weak and decreased very little following RA treatment. No difference was found for the expression of cdk2 and cyclinE mRNA before and after RA treatment. Conclusions: There is a functional link between RA and p27 Kip1 function in the control of neuronal differentiation in hNPCs. p27 Kip1 plays a key role during neuronal differentiation. Moreover, high levels of p27 Kip1 are regulated via increased p27 Kip1 mRNA expression.