We previously reported that the histologic grade of accidental involution of the thymus in infancy and childhood after a short period of acute illness correlates strongly with the duration of illness (Van Baarlen et al., Hum Pathol 1988;19:1155-60). We now extend this finding by reporting the phenotypic expression of thymus lymphoid and stromal cells. The thymic findings were correlated with changes in peripheral lymphoid organs. In the involuted thymus the immature and proliferating lymphoid populations that are present in the normal (uninvoluted) cortex were completely absent but the cortical epithelial network remained essentially intact even with increasing histologic grades of involution. Cells expressing the phenotype of subcapsular and medullary epithelium were found in this cortical stroma. In the subcapsular area, loss of expression of thymosin components alpha 1 and beta 4 was observed, without loss of epithelial cells. In the medulla a loss of cells expressing HLA-DR was observed, probably reflecting a loss of interdigitating cells. There was no correlation between changes in the thymus and peripheral lymphoid organs.