Over forty years ago Phoenix and his colleagues (Phoenix et al,1959) proposed an heuristically valuable concept, namely that one can view gonadal hormone action on the brain as anactivationaleffect, i.e., a transient modification of neuronal function, or anorganizationaleffect, i.e., a permanent modification of neuronal function — at some level. In the subsequent years much has been learned about the organizational effects of gonadal hormones which appear to be responsible, at least in large part, for the normal masculinization and defeminization of the brain of the male of a given mammalian species. Enough has been learned, in fact, to challenge current clinical practice in cases of ambiguous or underdeveloped genitalia in the newborn human infant. The goal of this discussion is to bring clinicians up to date about our current understanding of hypothalamic imprinting by gonadal hormones or, perhaps the more precise concept of the sexual differentiation of the brain, focusing on the laboratory rat as a model system. Laboratory rats are clearly not human beings, perhaps not even wild rats, but they are mammals as are human beings and have been studied extensively and provide a wealth of basic information with which to interpret the limited data from human subjects.