In the present study, based on 24 individuals aged 5-61 years, the histological pattern of the thymus has been determined and correlated to the thymus lymphocyte in-vitro responses to phytohaemagglutinin (PHA) and concanavalin A (Con A). It has been found that lymphocytes from histologically involuted thymus were significantly more responsive to PHA and Con A stimulation than lymphocytes from histologically normal thymus. These data indicate that thymus age-dependent involution is associated with increased lymphocyte in-vitro reactivity. In addition, in 10 cases the relative proportions of the thymus lymphocyte subpopulations have been determined by the use of monoclonal antibodies OKT3, OKT4, OKT6 and OKT8. These results have been correlated to the histology of the organ and to the mitogen responsiveness of thymus lymphocytes. In normal thymus the majority of the cells were OKT6+, while there were lower numbers were OKT3+. However, in involuted thymus, OKT3+ lymphocytes prevailed over OKT6+ cells. Furthermore, a direct relationship between the proportion of OKT3+ lymphocytes and the response to mitogens has been observed. These findings indicate that the increased mitogen response noticed in histologically involuted thymus is accompanied by an OKT3+-cell enrichment which is paralleled by a depletion of OKT6+ cells.