AbstractThe membrane mobility agent A2C accelerates the onset of the acrosome reaction of guinea pig spermatozoa by promoting capacitation. Spermatozoa incubated in a suspension of A2C particles in Ca2+‐free medium for one hour undergo a synchronous, rapid acrosome reaction upon the addition of Ca2+. These acrosome‐reacted spermatozoa are capable of fertilization as assessed by their ability to penetrate (fuse with) zona‐free hamster eggs.The disulfide‐reducing agent, dithiothreitol (DTT) inhibits A2C‐mediated capacitation. It also blocks fertilization of zone‐free eggs by acrosome‐reacted spermatozoa by preventing attachment of the spermatozoa to the egg plasma membrane.The mode of A2C action on spermatozoa is compared to that of A2C‐induced fusion in somatic cells. The similarity of the molecular events in the sperm membrane during capacitation and the acrosome reaction to these in other fusion events is pointed out.Inhibition of capacitation by DTT points to the importance of membrane and/or submembrane proteins and thiol groups in this process. Oxidation of sperm membrane SH groups may play an important role in in vi