A nonmetastatic, transplantable Leydig cell tumor of Fischer rats causes hypercalcemia in the host animals. The tumor's effects on long bones were studied with histochemical and morphometric methods. Small viable fragments of the tumor (about 1 cu mm) were transplanted into 59 Fischer rats. After 2 weeks, when the animals were sacrificed, the tumors weighed 13.9 +/- 4.8 gr (SD), and the animals had lost a mean of 10.1 g of weight. Compared with 16 normal control rats (mean weight gain of 9.5 g), the tumor-bearing rats showed: 1) a reduction in the volume of trabecular bone, which correlated well with the weight of the tumor; 2) a significant narrowing of the epiphyseal plate cartilage; 3) a diminution in the number of marrow fat cells, which in most tumor-bearing rats were totally absent; 4) an increase in the number of osteoclasts many of which were mononuclear and had to be identified with the aid of a histochemical reaction for acid phosphatase; 5) a great expansion of the marrow vascular channels that maintained an endothelial lining. Since there is no metastasis of the tumor cells, the effects of the tumor are presumably mediated by a humoral factor that activates existing osteoclasts and induces monocytes to differentiate into osteoclasts.