The Harderian gland of the green frog contains mast cells. Their number shows annual variations, being more numerous in the winter months. The increase of mast cell number (MCN) is matched by a marked degranulation. No sex differences are found throughout the year. Manipulations of the photoperiod and temperature, either in winter or in summer, suggest that only the latter is responsible for the annual variations. Exposure to higher temperatures causes a decrease in the MCN in the winter frogs, while exposure of the summer frogs to low temperatures provokes the opposite effect. The pituitary gland also influences MCN. Hypophysectomy causes a decrease of MCN, with a return to normal following replacement therapy with homologous pars distalis homogenate. Among pituitary hormones, only ACTH mimics the effect of pars distalis homogenate. However, a possible link seems to exist between environmental (temperature) and hormonal (pituitary) factors, since hypophysectomy prevents the increase of MCN in the summer frogs exposed to low temperatures.