We studied the effects of PS-K, a protein polysaccaride isolated from a basidiomycete, on the formation of blood-borne metastases. Experimental tumors were fifth-generation isotransplants of a spontaneous C3Hf mouse squamous cell carcinoma that was weakly antigenic. A single-cell suspension from fourth generation tumors was transplanted, and the tumor-bearing legs of the mice were amputated when transplants reached a certain diameter. Daily administrations of PS-K followed immediately, and both lungs were excised on the 21st postamputation day. The number of lung colonies formed on the surfaces of both lungs was counted and total volumes of metastatic colonies were estimated. PS-K, if administered alone, did not inhibit the lung colony formation. Marked reduction in this formation was observed when five daily doses of PS-K were administered simultaneously with cyclophosphamide. These observations indicate that PS-K may be a potent agent in the therapy of cancer if used as an adjuvant to a chemotherapeutic agent.