Nerve growth factor (NGF) and its signal-transducing receptor TrkA are expressed in the thymus. However, their possible role during thymic organogenesis is unknown. Here we analyze the thymus of trkA-kinase deficient 2-week-old mice. trkA-kinase +/+ and +/- mice had a normal thymus, whereas the thymus of trkA-kinase -/- mice showed lack of delimitation between the cortex and medulla, lower thymocyte density, and the presence of epithelial cell islands and numerous cysts lined with endodermal epithelium. The present results indicate that TrkA is necessary for the normal development of the thymus, and that its absence causes an arrest in the differentiation of endodermal epithelial cells. Whether this lack of differentiation has functional implication has yet to be determined.