Although undisturbed primary mouse mammary tumors may give rise to overt metastases, these have generally been observed near the terminal stage of progressive tumor growth. Unlike malignant breast disease in women, metastases are seldom the cause of death in mice, and in some strains as few as 2% of mammary tumor hosts may be affected (1). Highly metastatic tumors may, of course, be found, and hosts of the mammary carcinoma WHT all develop metastases (2). Evidence from animal models suggests that host defense reactions against immunogenic tumors may affect the incidence of metastatic spread (3-5). But nonimmunogenic and weakly immunogenic tumors probably represent the majority of mammary carcinomas (2, 6, 7), and this class was once considered outside control by the host. However, natural protective factors are also known which may prevent metastasis independently of specific antitumor immunity (8-10). There are therefore most likely several different biological factors and mechanisms which prevent circulating, viable cancer cells from developing into metastases. But one can not yet generalize whether natural resistance factors or induced resistance factors are the most important, or whether any resistance factors are as important in preventing metastases as is the basic unacceptability of cells in heterotopic locations. This review will not attempt to present a comprehensive analysis of cell-mediated and humoral immunity to mouse mammary tumors because this topic has recently been exhaustively treated in the reviews by Stutman (11) and Blair (12). We will focus primarily on information from in vivo investigations of the role of host resistance in the control of mammary tumor cells progressing through successive levels of metastasis from the primary tumor, through lymphatic or hematogenous dissemination, to colonization of distant organs.