The thymus plays a central role in the differentiation of T-lymphocytes. During the past years several in vitro models have been developed for the elucidation of the functional role of different thymic stromal cells. After reviewing the literature, the authors discuss: a) the in vivo and in vitro data on the structural organization of the thymus microenvironment, with particular reference to the epithelial cells; b) the endocrine function of the thymus; c) the interaction between the thymic epithelium and T-cell precursors. The experimental approaches to these problems are also discussed. In particular, the authors examine in detail the experimental aspects which are at present under investigation in their laboratories.