We have investigated the possibility of an interaction between epinephrine and external potassium in the stimulation of the hamster sperm acrosome reaction and in vitro fertilizing ability. We have found that: 1) K+ is required late in capacitation and/or the acrosome reaction, but is not required for penetration of the zona pellucidae, 2) the presence of epinephrine (50 microM) in the capacitation medium lowers the K+ requirements of these processes and 3) furosemide, a cotransport inhibitor, blocks the acrosome reaction, in vitro fertilization, and inhibits the stimulation by epinephrine. These results support the idea that there is an interaction between epinephrine as a stimulus to the secretion of the acrosomal content, and K+ as a mediator of the stimulus signal. They further suggest that K+ influx through the cotransport mechanism occurs during capacitation, that this mechanism is activated late during the process, and that it probably mediates the stimulatory effects of epinephrine. We would like to propose that the activation of passive cation transport mechanisms is a general phenomenon in biological signal transduction.