By in situ hybridization, we show the ability of human neuroblastoma SY 5Y cells to synthesize apolipoprotein E (apoE) mRNA. This synthesis varied during cell NGF-differentiation: the mRNA level decreased during the first 4 days of NGF treatment (NGF 4 days) and then increased during the 3 following days (NGF 7 days). Furthermore, a treatment of 4-day NGF differentiated cells with exogenous apoE during 3 additional days induced a clear decrease in apoE mRNA synthesis when compared with control cells. This effect was more or less pronounced according to the apoE tested variants: apoE4 was more efficient to decrease the apoE mRNA synthesis as compared with the control cells than apoE3 which was itself more efficient than apoE2. These results suggest that apoE mRNA synthesis in human neuronal-type cells could be regulated by different mechanisms such as those induced by NGF- and apoE-treatments.