Previous studies have indicated that hormone-responsive mammary tumors of GR mice are mixed populations of hormone-dependent and autonomous cells. We have now investigated whether these two cell types differ in susceptibility to cytostatic treatment. Experiments in which cyclophosphamide was injected in tumor-bearing mice did not reveal significant differences in percentage of inhibition between hormone-dependent, hormone-responsive, and hormone-independent tumors. Furthermore, the estrogen and progesterone receptor contents of the residual tumor masses after cyclophosphamide treatment were about the same as those of untreated tumors. When the cytostatically treated tumors were transplanted, the degree of hormone responsiveness of the transplants did not differ from that of transplants derived from untreated tumors, nor did their hormone receptor contents. These results indicate that the hormone-dependent and autonomous cells of GR mouse mammary tumors are inhibited to similar extents by cyclophosphamide. The possible significance of these results for combined endocrine therapy and chemotherapy is discussed.