(NZB x SJL)F1 (NS) female mice develop a marked hypertrophy of the thymus in the course of aging. The age-dependent evolution of the intrathymic lymphocyte population of these mice was monitored in comparison with that of the immunologically normal BALB/c and C57BL/6 strains. The expression of several lymphocyte markers on the surface of the thymic cells was quantitated using single- and two-color flow cytofluorometry analysis. Two main cell types could thus be identified in the thymus of 3-month-old mice: a major subset of bright Thy-1+, Lyt-1+2+, bright peanut agglutinin (PNA)+ lymphocytes and a minor subset of dull Thy-1+, Lyt-1+2-, dull PNA+ lymphocytes. In BALB/c and C57BL/6 mice, the frequencies of these cell types did not significantly vary between 3 and 18 months of age, despite a drop of thymic cellularity. In contrast, in NS female mice the proportion as well as the absolute number of dull Thy-1+, Lyt-1+2-, dull PNA+ cells increased while those of bright Thy-1+, Lyt-1+2+, bright PNA+ cells diminished during the same period. The emergence of new cell types could also be noted in the thymus of aging NS female mice. Thus, in addition to the appearance of dull PNA+, Lyt-2+ cells and of bright PNA+ cells devoid of T cell markers, there was a high frequency of non-T cells bearing surface immunoglobulin, Ia antigen and receptors for Fc. These data indicate that the thymic hypertrophy of NS female mice reflects the intrathymic accumulation of large numbers of phenotypically mature T and B cells. Such alterations were not detectable in NS male mice.