The molecular mechanisms underlying the pathogenesis of Wilms' tumor (WT) are poorly understood, although a variety of growth factors including platelet-derived growth factor and insulin-like growth factor are expressed and are thought to contribute to tumor development. In earlier studies, WT cells in culture were found to express the low affinity nerve growth factor receptor, p75. These WT cells were capable of responding to the neurotrophin (NT) NGF, suggesting that NT may be involved in WT pathogenesis. We have examined a group of WT immunohistochemically with antibodies recognizing known trk receptor proteins, the p75 receptor, and the NTs, NGF and NT-3. Confirmatory immunoprecipitation and Western blots were then performed on representative WT samples from the study group. The p75 receptor was found predominantly in the epithelial and blastemal components where high levels of NT were also identified. The trk A and B receptors were primarily within stromal components, whereas the trk C and C' receptors were present within epithelial structures. Western blot analyses confirmed the presence of the respective receptor proteins with variations correlating in some cases with histological type. The selective presence of NT receptors and growth factors in this series of WT implies autocrine/paracrine mechanisms for tumor development.