Apoptotic cell death plays a critical role in the development of the nervous system. Although the apoptotic death of mature non-dividing neurons has been extensively studied, the mechanisms mediating the extensive cell death in areas of the developing brain where proliferating neuroblasts are differentiating into mature neurons have not been analyzed. We have previously shown that the cell cycle arrest of a proliferating neuronal cell line by transfer from medium containing 10% foetal calf serum (FCS) to serum-free medium results in the morphological differentiation of some cells and the death of others by apoptosis. Here we show that the effect of 10% FCS can be mimicked by medium containing either similar concentrations of newborn or adult bovine serum or 1% FCS all of which maintain cellular proliferation and inhibit differentiation and apoptosis. In contrast, the presence of 0.5% FCS in the medium effectively prevents apoptosis but does not allow cellular proliferation or inhibit morphological differentiation. Hence cell cycle arrest and differentiation can occur in the absence of apoptosis in cells of neuronal origin and the factors in serum responsible for modulating these processes are likely to be distinct.