In vivo, guinea pig spermatozoa do not begin to undergo the acrosome reaction and to penetrate eggs until 4 to 10 h after they are deposited in the female genital tract. When spermatozoa are incubated in a modified Krebs-Ringer’s solution containing 0.003 percent Hyamine, the majority of them exhibit both the acrosome reaction and activation within 10-15 min and become capable of penetrating eggs. The acrosome reaction and activation induced by Hyamine are reversibly blocked when calcium ions are omitted from the medium. Other reagents capable of inducing an accelerated acrosome reaction and/or activation include: Triton, Brig, saponin, nonanol, nystatin, mersalyl acid, dibucane, procaine, neotetrazolium chloride, nitro blue tetrazolium, chloroquine, calcium ionophore, unheated sera of the rabbit and guinea pig, rabbit complement and pronase. The study shows that guinea pig spermatozoa are potentially capable of an immediate acrosome reaction and activation upon leaving the epididymis.