MCF-7 is a human breast cancer line which requires estradiol supplementation for growth in s.c. tissues of athymic mice. In order to evaluate the influence of host site on hormone-dependent tumorigenicity and growth, MCF-7 cells were inoculated into tissues varying in ability to concentrate exogenous estradiol. Tumorigenicity was defined in terms of latency, threshold inoculum size, and tumor growth and progression. We observed that sites such as lung rarely supported MCF-7 tumors. However, moderately estrophilic sites such as mammary fat and adjacent subcutaneum and dermis supported the growth of small MCF-7 tumors from large tumor cell inocula, but only in estrogenized mice. In contrast, the highly estrophilic sites, brain and periuterine tissues, produced rapidly growing tumors from small tumor cell inocula. Only in periuterine tissues did tumors develop in the absence of exogenous estradiol. These studies demonstrate that tumorigenicity and growth rates of estrogen-dependent MCF-7 tumors vary as a function of tissue implantation site.