Rana pipiens were divided into four groups: controls; hypocalcemic frogs, depleted of salts by acclimation to deionized water; hypercalcemic frogs, calcium-loaded by the introduction of 40 ยตmol calcium gluconate; and frogs exposed to the potential competing ions Mg 2+ , Sr 2+ , and Ba 2+ . All groups displayed calcium influx that was proportional to external [Ca 2+ ]; however, the group acclimated to deionized water also displayed hypocalcemia (P < 0.025) and enhanced Ca 2+ influx at higher (>0.3 mM) external [Ca 2+ ]. Ca 2+ efflux was depressed in hypocalcemic frogs, and thus net Ca 2+ flux shifted from net loss in control frogs to net uptake in hypocalcemic frogs. Hypocalcemia also resulted in increased skin Ca 2+ deposits which may be related to a decreased Ca 2+ (and other ions) permeability as a consequence of the acclimation to deionized water. Another group of frogs was Ca 2+ -loaded by injecting calcium gluconate. Sodium gluconate controls did not significantly alter Ca 2+ fluxes. The frogs that received calcium gluconate treatments became hypercalcemic (P < 0.01) and did not display significant changes in calcium fluxes, nor did they show significant changes in skin calcium deposits. We conclude that hypocalcemia leads to regulatory responses that stimulate active Ca 2+ transport in Rana pipiens skin and possibly inhibits cutaneous and renal efflux. We also conclude that hypercalcemia does not alter calcium fluxes across skin. The ions from Group IIA of the Periodic Table of Elements had little effect on Ca 2+ fluxes at concentrations ranging from 0.5-4.0 mM; neither Sr 2+ or Ba 2+ affected Ca 2+ influx. The only divalent ion tested that influenced Ca 2+ was Mg 2+ , which significantly inhibited Ca 2+ influx but only at 4.0 mM or eight times the external [Ca 2+ ]. We conclude, therefore, that the Ca 2+ transport mechanism is fairly specific for Ca 2+ within Group IIA.