Fish gills are a primary target of metals from the external environment and serve as a major route for metal uptake. After 12-h exposures to 1 mu M Cd-109, Zn-65, or Cu-64 in ''Ca2+-free'' water, gills concentrated metals 3 to 11-fold and contained 38-50% of the total metal burden while sustaining only minor epithelial damage. A twofold increase in chloride cell (CC) surface area had no effect on Cu uptake and actually decreased Zn uptake, confirming that CCs are not primarily involved in the uptake of either metal. In contrast, Cd uptake increased with CC proliferation. Autoradiography revealed a high degree of localization of Ca-45 in chloride cells confirming their primary role in Ca2+ uptake, whereas Cd and Zn were uniformly distributed amongst all gill epithelial cells. Because CCs did not specifically accumulate Cd-109, we propose that other effects of softwater acclimation were responsible for the increased uptake of Cd. The only cells in the gills specifically accumulating Cd and Zn were eosinophilic granulocytes localized in the central sinus of gill filaments. Autoradiography of liver and kidney tissue showed uniform distribution of Cd-109 and Zn-65, i.e., there were no cells specifically accumulating metals in these tissues.