The incidence of metastasis of xenogeneic tumors transplanted to nude mice is controversial. We studied 106 malignant human tumor lines in a total of 1,045 nude mice, and observed metastasis in only 14 instances (1.3%), involving 11 different tumor lines. Three of the lines showed repeated metastasis. Breast tumor lines metastasized with significantly greater frequency than other tumor types. None of the sarcoma lines metastasized. Tumors derived from human metastases were no more prone to metastasizing in nude mice than were tumors derived from primary sites. However, deep penetration of the body wall during growth of the tumor transplant was highly correlated with metastasis (p<0.001). Such factors as nude mouse health, tumor size and growth rate, and age and sex of the host mouse were not correlated with metastasis. Serial passage in nude mice did not select for a more malignant tumor line, since the incidence of metastasis did not differ at various passage levels. Thus, metastasis of human malignant tumors in nude mice would appear to depend primarily upon the site of tumor growth in the nude mouse, and upon the intrinsic metastasizing capability of the tumor line employed.