T-cell differentiation is known to be mediated by lympho-stromal interactions. However, the precise role of cellular complexes formed during this process is far from clear. We have previously established a thymic medullary epithelial cell-line, E-5, and have shown the adherence of thymocytes by a receptor-mediated-mechanism. We report here that the thymocytes able of complex-formation with E-5 cells appear at day 16 of gestation. Moreover, while the proportion of such thymocytes is constant throughout post-natal life, their absolute number decreases with thymic involution. We have also investigated the influence of the genetic background of thymocytes on adherence and found that polymorphic regions of H-2 genes were not involved in contact recognition. Therefore, this type of lympho-stromal interactions is unlikely to participate in the education to self MHC-restriction. However, thymocytes from B6/lpr mice, which spontaneously develop systemic lupus erythematosus (SLE) and have impaired T-cell differentiation, were shown incapable of adhering to E-5 cells. These results are interpreted as showing that interaction between thymocytes and medullary epithelial cells reflect a discrete stage of T-cell differentiation.