Aging involves morphological and functional alterations within the microenvironment of the thymus where heterogenous populations of thymic epithelial cells (TEC) play the main roles. The studies performed to date on thymic involution signalize a disturbed interaction between individual thymic compartments that disrupt thymocyte-TEC interactions and, as a sequele, disturb differentiation of both TEC and thymocytes. The process of aging affects the various subsets of TEC at different periods of life. Changes in different subsets of TEC are documented on the basis of their phenotypical characteristics, involving morphological analysis and immunocytochemistry. The character and kinetics of changes in TEC are typical for individual subsets and probably sex-dependent. In the course of life, the involutionary changes, expressed by disorganised thymic structure and function, are accompanied by changes in medullary TEC, manifested by alterations in the differentiation process of the cells. In parallel, at the same stage of individual life, the aging process induces increased proliferative and secretory activity of subseptal TEC, which seem to functionally replace medullary TEC. Structural and phenotypic modifications of TEC are locally controlled by complex sets of different factors and seem to represent a morphological adaptation of the gland to the process of aging. Microsc. Res. Tech. 62:488-500, 2003.