The purpose of this study was to investigate the effect of chlorambucil on the mouse Leydig cell by electron microscopy. Chlorambucil suspended in the 0.5N sodium bicarbonate(pH 8.0) was injected I.P.(intraperitoneal) at a dosage of level 20mg/kg for 1 weeks, 3 weeks and 5 weeks, respectively. The results obtained from this experiment are as follows: 1. One week after the administration of chlorambucil, there was an increase in heterochromatin, swelling and cristae disruption in some mitochondria, mild vacuolation between cells and the occurrence of membrane bound inclusions in some nuclei. 2. After 3 weeks, smooth endoplasmic reticulum dilations, cytoplasmic vacuolation, mitochondrial swelling, inner mitochondrial cristae disruption, membranous whorls, and intranuclear inclusions were observed in the treated cells. 3. After 5 weeks of treatment, most mitochondria were swollen and their membranes were severely disrupted. Further, smooth endoplasmic reticulum dilations and vacuolation of the cytoplasm were apparent in the treated Leydig cells. In addition numerous membranous whorls and intranuclear inclusion bodies were present. The nuclei displayed invaginatons of the nuclear membrane and large clumps of heterochromatin. From these results it is concluded the longer the duration of chlorambucil administration, the greater the degeneration of the nucleus and cytoplasmic organelles.