Intracellular free Ca2+ concentrations ([Ca2+]i) and membrane potentials were measured in mature human oocytes. Injection of cytosolic extracts made from human or hamster spermatozoa triggered oscillations in [Ca2+]i in human oocytes similar to those described previously in mouse and hamster oocytes. In contrast, injection of carrier buffer caused no [Ca2+]i increase and injection of Ca(2+)-containing solutions caused only a single [Ca2+]i transient. Injection of human sperm extracts also triggered [Ca2+]i oscillations in mature mouse oocytes. The [Ca2+]i oscillations in human oocytes were accompanied by hyperpolarizations in membrane potential. Perfusing oocytes with the sulphydryl reagent thimerosal also caused oscillations in the free [Ca2+]i concentration simultaneously with membrane potential hyperpolarizations. These data suggest that human oocytes possess a similar mechanism for generating [Ca2+]i oscillations to those described in other mammalian oocytes and a membrane potential response similar to that seen previously specifically in hamster oocytes. The data also support the view that human oocytes are activated at fertilization by diffusion of a protein from the spermatozoa into the ooplasm after gamete membrane fusion.