Steroid/thyroid actions in the brain are exerted through their receptors which belong to the nuclear receptor superfamily. Transcriptional transactivation mediated by these receptors depends on recruited co-activators, among which steroid receptor co-activators (SRCs) seem to be restricted to the nuclear receptor family. By using Northern and Western blot analysis we have estimated the mRNA and protein levels, respectively, of SRC-1 in the brain and pituitary of male and female rats, under physiological conditions and following restraint stress. Under basal conditions, SRC-1 is expressed at higher levels in the hippocampus and the pituitary of male, compared to female rats. Acute stress results in decreased, compared to the control, SRC-1 levels in the hypothalamus of both sexes, in the pituitary and frontal cortex of male rats, and in increased SRC-1 levels in the hippocampus of female rats. The observed changes at the mRNA level are supported by analogous changes at the protein level. The apparent regulation of SRC-1 gene expression in the nervous system by the endocrine status of the animal, adds another level of complexity in the mechanism controlling steroid hormone actions. Furthermore, the variability in SRC-1 expression within the brain provides a means to explain the cell-specificity of steroid hormone actions in this tissue.