Previous studies have shown that malnutrition severely affects both lymphoid and epithelial components of the thymus. Yet, few data are available concerning the extracellular matrix (ECM) of the thymic microenvironment in malnutrition. We studied by histological, ultrastructural, and immunohistochemical means thymuses obtained in necropsies from 19 malnourished children. We observed a consistent increase in the intralobular ECM-containing network which could be ascertained histologically by the dense reticulin staining. This abnormally dense ECM network contained fibronectin, laminin, and type IV collagen. Importantly, the enhancement of thymic ECM in malnourished individuals positively correlated with the degree of thymocyte depletion. This correlation may represent a cause-effect relationship in which the contact of thymocytes with abnormally high amounts of thymic ECM triggers and/or enhances programmed cell death.