Metallothioneins (MTs) are a family of low molecular weight proteins which in rodents comprise four isoforms (MT-I to -IV). MT-I+II are widely expressed isoforms which are highly inducible by factors such as heavy metals and a number of hormones. The expression of these isoforms in the brain has been regarded as basically astrocytic, and to a lower extent, neuronal. We, however, demonstrate in this report, by radioimmunoassay and immunocytochemistry, that MT-I+II are expressed in primary cultures of rat microglia and that, furthermore, they are inducible by zinc and copper. Thus all major brain cell types may express the MT-I+II isoforms and respond with increased protein levels to physiological stimuli such as increased extracellular zinc and copper content. In contrast, microglia MT-I+II levels are not affected by either the glucocorticoid dexamethasone or the cytokine IL-1 under the experimental conditions.