The effects of inoculation site and dietary fat intake on the growth and metastasis of the MDA-MB-435 human breast cancer cell line were studied in athymic nude mice. The tumor cells, 1 x 10(6), were injected into either a right-sided thoracic or inguinal mammary fat pad (mfp), and 1 week later mice were randomly assigned to a high-fat (HF), 23% corn oil, or a low-fat (LF), 5% corn oil, diet. There were 30 mice in the HF, and 30 in the LF subgroups from each of the two inoculation site groups. The experiment was terminated 15 weeks after the tumor cell inoculations. Within the thoracic mfp-injected group, a HF diet reduced latency, increased growth rate at the primary site, and enhanced metastasis to regional lymph nodes, lungs, and intra-abdominal sites. For mice inoculated into an inguinal mfp, fat intake affected neither primary nor metastatic tumor development and growth; in both subgroups lung metastasis was significantly less than in the HF-fed, thoracic mfp-injected subgroup. The histological features of the lung metastases were consistent with a vascular mode of spread, whereas the extensive intra-abdominal lymph node involvement observed in mice with inguinal mfp tumors was in keeping with lymphatic-borne metastases.