The reduction of desmosterol by cell‐free preparations from developing rat brain was established and the age‐dependent alterations in reductase activity were correlated with levels of desmosterol in brain. An increase in enzymic activity followed closely the sharp increase in levels of desmosterol that was observed at about 5 days of age and that reached a maximum at 8‐11 days of postnatal age. Furthermore, the abrupt decrease in the desmosterol content of brain at 13‐15 days of age was associated with a decrease in enzymic activity. We suggest that the enzyme may be substrate‐induced and that this attribute may be of significance with respect to the ontogenesis of myelin. Cerebral desmosterol reductase exhibited a specific requirement for NADPH and was primarily a particulate enzyme.