Research on testicular toxicology has been advanced significantly by the introduction of in vitro testing systems. In vivo systems, however, are still essential parts of the risk assessment process, and they are unlikely to be eliminated by in vitro model systems. While in vivo systems are needed to study the integrated male reproductive system, in vitro systems are uniquely suited to investigate specific mechanisms of action in the testis. In vitro systems substantially improve the interpretation and use of in vivo systems. In vitro models can be used alone or in combination with each other to test hypotheses about testicular toxicity. Numerous systems are described in the literature, including Sertoli-germ cell cocultures, Sertoli cell-enriched cultures, germ cell-enriched cultures, Leydig cell cultures, and Leydig-Sertoli cell cocultures. These systems have been used to test relative toxicologic activity of selected chemicals in a class, to investigate the cellular response to certain toxicants, to study the metabolic capability of cells, and to describe the interaction of adjacent cell types.