Immediate post-receptor events following alpha-adrenoceptor stimulation in cardiac ventricular muscle are still largely unknown. Since membrane redox systems appear to be present in cell plasma membranes and may be involved in trans-sarcolemma electron efflux, the possibility that Ca2+ inflow was controlled by electron efflux was explored. Electron efflux was measured by monitoring the rate of reduction of extracellular ferricyanide (a non-permeant anion) and compared with changes in contractility of the perfused heart as an indirect assessment of altered cytoplasmic Ca2+ concentration. Alpha-agonists significantly increased the rate of ferricyanide reduction by approx. 42%. Activation was dose- and time-dependent and closely accompanied changes in contractility either when the alpha-agonist was added or removed. Perfusion of the heart with sufficient Ca2+ chelating agent to prevent beating, did not affect the rate of ferricyanide reduction, but amplified the stimulatory effect of methoxamine on this rate. Kinetic assessment indicated that alpha-agonists led to an increase in the number of electron efflux sites in the ventricular sarcolemma. Neither diacyl glycerol nor the Ca2+ ionophone A23187 or a combination of the two had any effect on electron efflux rates. It is proposed that alpha-adrenoceptor stimulation promotes Ca2+ entry into the heart cell by directly activating the rate of electron efflux. An accompanying outward release of protons from localized regions of the sarcolemma (Ca2+ channels?) may then facilitate a 1-for-2 inward movement of Ca2+.