Heparin, cortisone, and combination of these two drugs were used for treatment of solitary tumors and artificial lung metastases of the fibrosarcoma NFSA and the mammary carcinoma MCA-K in C3Hf/Kam mice. Heparin reduced the number of artificial metastases of both tumors, but it did not affect the s.c. growth of these tumors. Conversely, cortisone reduced both the number of artificial metastases and the growth rate of s.c. tumors. The effect of cortisone was not further influenced by heparin. Cortisone showed a tendency for causing enhancement of spontaneous metastases. In addition, two heparin analogs, hexuronyl hexaminoglycan sulfates were studied against MCA-K solitary tumors and their spontaneous metastases. They were ineffective when given alone, and they did not influence the effect of cortisone on the s.c. tumor growth. However, they slightly reduced the cortisone-induced enhancement of spontaneous metastases.