SP-10 is a sperm-specific, intra-acrosomal protein that is considered to be a vaccine candidate for immunocontraception. In the present study, in situ hybridization with biotin and 35S labeled riboprobes was used to determine the pattern of SP-10 mRNA expression in human testes. Both methods demonstrated SP-10 mRNA primarily in round spermatids found in stages I, II, and III of the seminiferous cycle. Morphometric analysis of silver grains with the 35S-labeled probe showed less SP-10 mRNA in spermatids at stages IV, V, and VI than in previous stages, and rarely was label found in spermatogonia or spermatocytes. The expression of SP-10 mRNA first appeared at stage I coincident with the appearance of the protein, which was shown previously to persist in the acrosomal matrix throughout spermiogenesis. The decrease in SP-10 mRNA occurred when spermatids underwent polarization, nuclear condensation, and elongation. The appearance of SP-10 mRNA in round spermatids suggests that increases in SP-10 transcription or SP-10 mRNA stability or both occur as spermatids develop from the Golgi phase to the cap phase. The subsequent decline of SP-10 mRNA, despite the persistence of the SP-10 protein in all spermatids, suggests that a decrease in SP-10 transcription or an increase in mRNA degradation occurs when spermatids elongate.