The addition of egg jelly to sea urchin sperm induces multiple changes in morphology and behavior. When jelly is added to sperm diluted in seawater, the acrosome reaction is triggered, the mitochondrion rounds up, the internal pH is transiently alkalinized and then reacidified, and respiration becomes uncoupled and rapidly decreases. Sperm also become unable to fertilize eggs within a few minutes after jelly addition. In order to explore in more detail the effect of egg jelly on sperm, we have studied the response to jelly in the presence of inhibitors of the acrosome reaction. When jelly is added to sperm under conditions which are inhibitory for the acrosome reaction, an alkalinization takes place without the subsequent reacidification, the mitochondria remain coupled, and respiration and intracellular ATP levels remain high. Sperm viability is prolonged by some of these conditions, but not others. The addition of jelly to sperm in the absence of calcium elicits an internal alkalinization but no other rapid change in sperm physiology. The capacity of egg jelly to alter sperm physiology even when the overall acrosome reaction is inhibited indicates that some of the physiological changes either are early events in the triggering pathway that happen before the inhibitory step or are unrelated to the acrosomal reaction itself. The reacidification of the internal pH, the uncoupling and decrease of the respiration, and the decrease of the ATP levels might be linked together by the large influx of calcium that occurs after the acrosome reaction.