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In previous works we reported the finding of neurotrophic activity in a serum-free Dulbecco's modified Eagle's medium conditioned by rat sciatic nerves, previously maintained in culture for 11 days. This medium produces rapid neuron-like differentiation of cultured PC12 cells, as revealed by an increase in the size of the cell body and by the extension of short and/or long neurites by most of the cells. Neuregulin present in the conditioned medium was demonstrated to play a key role in the observed differentiation. In the present work, taking into consideration those latter results, the neurotrophic activity of conditioned media prepared with sciatic and optic nerves cultured during days 1-4 and 9-12 were studied. Evaluation of the trophic activities of those media revealed an opposite timing in the activities of sciatic and optic nerves conditioned media. The activity of the sciatic nerve was not observed in the 1-4-day period, increasing then up to the 9-12-day period. On the contrary, the optic nerve conditioned medium was active in the 1-4-day period, decreasing down to the 9-12-day period. These results led us to explore the contribution of the different cellular constituents of those nerves to their neurotrophic properties. As a first step in that direction we also investigated the neurotrophic activity of media conditioned during 12 days by cultured Schwann cells isolated from rat sciatic nerves. The Schwann cell conditioned media did produce a rapid differentiation of the PC12 cells similar to that caused by the sciatic nerve conditioned medium, though of a lower magnitude. Variations in the trophic activities of the conditioned media used in the present work is discussed taking into consideration the production of trophic and inhibitory factors by the peripheral and central glial cells. The role played by the optic nerve glia and myelin is being investigated at present.