An ultrastructural survey of 11 human tumors passaged in N:NIH(S) (nu/nu) mice showed two instances of type C virus production. In one instance type C virus particles were observed in the endothelial murine stromal cell component of an embryonal carcinoma but not in the human tumor cells. In another instance type C virus particles were seen replicating in the chondroblastic human cells of a xenografted osteosarcoma. The type C virus produced in the human cells failed to transform NIH/3T3 cells, the C-127 rat cell line, or mink cells. Nucleic acid hybridization studies in which a human endogenous retroviral probe and a xenotropic murine leukemia virus envelope probe were used suggested that the retrovirus present in the human osteosarcoma cells is related to murine leukemia viruses. Intracisternal A-particles (IAP) were also detected in the human osteosarcoma cells. Their presence in the human cells was demonstrated by simultaneous visualization of IAP and human HLA determinants at the cell surface. The literature on type C virus infection of human cells and tumors grafted in nude mice is reviewed.