Many experimental studies concerning hypoxia or ischemia have reported a decrease in intra/extracellular pH and massive dopamine (DA) release in the striatum. The present work investigated whether the increase in striatal extracellular DA is related to acidification or to lactate production. Striatal perfusion of lactic acid (pH 5.5) by microdialysis in conscious freely-moving rats induced an increase in extracellular concentrations of DA and catabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), as a probable result of acidification. Perfusion with sodium lactate (pH 7.4) failed to modify DA and catabolite release, whereas orthophosphoric acid produced the same effect as lactic acid. As lactic acidosis is known to induce a displacement of iron from its uptake sites, the possible role of this metal in response to acidosis was studied by perfusing ferrozine, an iron complexing agent, at the same time as lactic acid. The results showed that ferrous ions are involved in the process and suggested that oxygen free radicals play a role in the extracellular release of DA. Thus, lactic acid perfusion in rat striatum would appear to be a useful model for in vivo studies of the mechanisms responsible for increases in extracellular DA during hypoxia and ischemia.