The biosynthesis of macrophage-migration inhibitory factor (MIF) and its regulation by the glucocorticoid dexamethasone was examined in cultured hippocampal and neocortical embryonic rat cells. Using immunohistochemical methods, MIF was found to be localized in neuronal as well as in non-neuronal cells. During the whole 12 day culture period, levels of MIF transcripts were detectable in both hippocampal and neocortical cells with an apparent increase in extracellular MIF protein at the later time points examined. Treatment with even very low concentrations (10(-11) M) of dexamethasone did not alter MIF mRNA levels but resulted in a rapid release of intracellular MIF protein within 1 and 4 h and a subsequent replenishment after 24 h. These data suggest that glucocorticoids do not affect the transcriptional activity of the MIF gene but induce the secretion of the protein, which suggests a close functional relationship of both mediators in the CNS.