We assessed the reproductive cycle of the venerid clam Meretrix lusoria by histological analysis of the gonads. Individuals for study were collected from natural populations on the Shirakawa tidal flat, Ariake Sound, and from populations that had been transplanted from the Shirakawa flat to the Oi flat in Tokyo Bay. In both study areas, the reproductive cycle was synchronized between sexes. Gonads of the clam started to develop in early spring and matured during the summer. Mass spawning occurred in the late summer/early fall. The clam matured at a shell length of 17–20 mm, which is much smaller than previously considered. While trophic conditions and salinity differed considerably in the two study areas, water temperatures showed similar seasonal changes (12°C during the winter and around 30°C during the summer). Thus, temperature probably controlled gonadal development. The coincidence of the period of spawning with the period of frequent intrusion of hypoxic waters into the tidal flats in Tokyo Bay suggests that such hypoxic events interfere with clam recruitment and are at least partly responsible for the disappearance of the natural population at this location.