AbstractIn prophase I‐arrested surf clam oocytes, fertilization is the normal trigger for resumption of meiosis, first evidenced by germinal vesicle breakdown (GVBD). Various artificial agents are able to induce GVBD and most of them require the presence of external Ca2+to be efficient. One exception to this rule is the reported possibility of inducing GVBD by an hypertonic treatment, using high concentrations of glycerol, in the complete absence of external Ca2+. We have investigated the processes underling glycerol‐induced activation and found that, under this condition, GVBD shows very slow kinetics and is not followed by any normal subsequent steps of meiosis, such as formation of metaphase chromosomes or polar body extrusion. Glycerol‐activated oocytes do not show the normal response in protein synthesis but they undergo increased protein phosphorylation which is inhibited by 6‐dimethylaminopurine (6‐DMAP), which also inhibits GVBD. We conclude that the hypertonic treatment by glycerol, in the complete absence of external Ca2+, induces a partial program of activation through increased protein phosphorylation but that the normal full response requires an increased Ca2+influx as triggered by other well‐known artificial activa