Surf clam (Spisula solidissima) oocytes, when shed, are at prophase I of meiotic maturation. Fertilization is the normal activation process leading to germinal vesicle breakdown (GVBD) and further steps of meiosis, followed by successive embryonic mitoses. We review here work suggesting that early rises in intracellular ca2+ and pH (pHi) are normally associated with oocyte activation. Experimental evidence suggesting a pivotal role for the ca2+ response and a more modest contribution of pHi are presented. The mechanisms of activation of Spisula oocytes by various artificial agents mimicking sperm are discussed in relation to their potential relevance to the physiological process of fertilization. We emphasize that serotonin-induced activation of Spisula oocytes is probably the best available model system to gain knowledge on the signal transducing systems stimulated by both serotonin or sperm. The potential physiological role of serotonin receptors present on oocytes is critically considered. Future perspectives and possible research directions are proposed to M e r elucidate the mechanism of oocyte activation in Spisula.