Experimental models of human neoplastic diseases are used in attempts to reconstruct events that occur in patients with cancer. Although in vitro systems provide a wealth of information about the cellular and molecular biology of tumor cells, they are inadequate for studies that address the complexities of human neoplasia pertaining to metastasis, experimental therapeutics, and immunity. Since the late 1960s, athymic nude mice have provided an opportunity to study the growth and, in some cases, the metastasis of xenografted human tumors in vivo. Recently, the availability of severe combined immunodeficient (scid) mice has provided an alternative model for studying human malignancies and has led to numerous reports of its distinct advantages over nude mice. When direct comparisons have been made, it has often been apparent that human tumors grow better and are more likely to metastasize in scid mice than in nude mice. Indeed, some human tumors which have never before been propagated in vivo will engraft in scid mice. Furthermore, the unique capability of scid mice to support human immunocompetent cells offers the potential to study the human immune response to tumors. This article outlines the current progress toward defining and using scid mice in models of human neoplastic disease. Characteristics which distinguish scid mice from nude mice are emphasized and a discussion of future prospects is included.