We have established a monoclonal antibody (mAb) AG7 defining a sperm acrosome antigen-1 (SAA-1) on spermatozoa from the human and several mammalian species. MAb AG7 inhibits fertilization of mouse eggs in vitro and in vivo. An important characteristic of mAb AG7 is its inhibition of the rise in intracellular calcium induced by progesterone in human spermatozoa. Here we show that, following the acrosome reaction, SAA-1 is lost from the cap of human spermatozoa but remains detectable in the equatorial region. Acrosome reaction assays demonstrated a clear difference between progesterone- and A23187-induced acrosome reactions. For induction of the acrosome reaction with progesterone, a minimum capacitation time of 6 h was required. A23187 induced the acrosome reaction regardless of capacitation time. MAb AG7 completely inhibited the progesterone-induced acrosome reaction, but not the A23187-induced acrosome reaction in human spermatozoa. Differences in the pattern of calcium flux induced by the two agents might account for this phenomenon. The inhibition of the progesterone-induced acrosome reaction by mAb AG7 implies a regulatory function of SAA-1 during the human sperm acrosome reaction.