Prostate cancer is the most common malignancy in American males and is second only to lung cancer as a cause of death in the United States. Clinically, radical prostatectomy offers a patient with locally contained disease an excellent chance for cure. For patients with metastatic disease, the current therapies are merely palliative. Understanding the biology of prostate cancer metastasis should facilitate the development of novel and effective therapeutic modalities. Crucial to this objective is the availability of human tumor systems in which the biology of metastasis can be studied. The present chapter will briefly assess various in vivo and in vitro approaches to study metastasis in human prostate cancer. Utilization of athymic nude mice has played an important role in maintaining human prostatic cancer cells as xenografts and has provided an opportunity to establish site-specific subpopulations of the parental cell lines for further characterization and investigation. At present, a few established cell lines have been useful for this purpose. Fresh tumor specimens, unfortunately, have shown limited ability to grow in nude mice. The recent development of novel approaches to permit the maintenance of freshly harvested prostate cancers has been encouraging. The use of reconstituted basement membrane (Matrigel) for co-injection with cancer cells into the subcutaneous tissues has supported growth of biologically indolent tumors. Another approach is to administer tumor cells orthotopically into the prostate of recipient nude mice. Bone marrow metastases in nude mice have been rare in the past. Recently, three approaches have been shown to be successful in accomplishing bony metastasis with PC-3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)