Sperm-zona adhesion is an essential event in mammalian fertilization, failure of which causes sterility. However, the molecular mechanisms involved in this process are still poorly understood. It has been suggested by few laboratories studying gamete interaction that acrosomal molecules are implicated in sperm-zona pellucida adhesion prior to the acrosome reaction (AR). Zonadhesin, a sperm-specific protein located in the acrosome is critically involved in zona binding. Here we describe the cellular and molecular interaction of zonadhesin during fertilization and also discuss its role in species-specific gamete interaction--an intriguing question in biology. We propose a model in which sperm could transiently expose acrosomal molecules that adhere to the zona independently of the AR in a 'kiss and run' mechanism. This could be a valuable framework for further investigations and a detailed understanding of the molecular events during gamete adhesion is likely to provide new approaches for the design of more effective male contraceptives and better diagnostic methods for sperm dysfunction.