1. The release of [3H]dopamine (DA) in response to inhibition of the Na+ pump or to intracellular acid load was studied in rabbit carotid bodies (CB) previously incubated with the precursor [3H]tyrosine. The ionic requirements of the release response and the involvement of specific ion transport systems were investigated. 2. Inhibition of the Na+ pump, by incubating the CB with ouabain or in K(+)-free medium, evokes a DA release response which requires the presence of Na+ and Ca2+ in the medium and is insensitive to nisoldipine. This suggests that the response is triggered by entry of external Ca2+ through Na(+)-Ca2+ exchange, a consequence of the increase in intracellular Na+ resulting from inhibition of the pump. 3. Incubation of the CB in medium equilibrated with 20% CO2 at pH 6.6, or in medium containing the protonophore dinitrophenol (DNP) or the weak acid propionate, elicits a DA release response which requires also the presence of Na+ and Ca2+ in the medium and is insensitive to dihydropyridines. 4. Ethylisopropylamiloride (EIPA), an inhibitor of the Na(+)-H+ exchanger, markedly decreases the release response elicited by DNP or propionate in bicarbonate-free medium, but has not any effect in bicarbonate-buffered medium. In the latter condition, the EIPA-insensitive release of DA is inhibited by reducing the HCO3- concentration in the medium to 2 mM or by removal of Cl-, suggesting that in bicarbonate-buffered medium a Na(+)-dependent HCO3(-)-Cl- exchanger is involved in the release response. 5. It is concluded that the release of DA by the chemoreceptor cells in response to acidic stimulation is triggered by entry of external Ca2+ through Na(+)-Ca2+ exchange. This exchange is promoted by the increase of intracellular Na+ that results from the operation of Na(+)-coupled H(+)-extruding mechanisms activated by the acid load.