A mutant strain of rat, LEC, shows a novel arrest of T-cell maturation from CD4+8+ to CD4+8−, but not to CD4−8+ cells in the thymus. The responsible mutant locus is designated the thid, which was acted upon in a recessive manner of inheritance. We found that LEC rat thymocytes failed to respond to interleukin (IL)-1, IL-6 and IL-7 in the presence of the mitogenic lectins, Allo A or concanavalin A (Con A). The unresponsiveness appeared to be due to unresponsiveness to the lectin stimulation rather than because of cytokine stimulation. Normal rat CD4−8+/− (consisting of CD4−8+ and CD4−8− thymocytes), CD4+/−8− (consisting of CD4+8− and CD4−8− thymocytes), and CD4−8− thymocyte subsets normally responded to mitogenic stimulation, while CD4+8+ thymocytes did not. In contrast, all LEC rat CD4−8+/−, CD4+/−8−, CD4−8− and CD4−8+ thymocytes did not respond to the mitogenic stimulation, suggesting that the unresponsiveness of the CD4−8+/− thymocytes seems to be responsible for the unresponsiveness of whole thymocytes in LEC rats. LEC rat CD4−8+/− thymocytes normally expressed Con A receptor (R), lymphocyte function-associated antigen-1 (LFA-1), and CD45, which are thought to be important molecules for lectin stimulation. When backcross rats from (F344 × LEC)F1 × LEC were examined, the phenotype for the thid mutation correlated with the [3H] thymidine deoxyribose (TdR) incorporation level in response to Con A stimulation; thymocytes from backcross rats showing +/thid phenotype responded to Con A stimulation normally, whereas thymocytes from backcross rats showing thid/thid phenotype showed significantly lower responsiveness compared with +/thid rats. However, in WKAH.C-thid congenic rat thymocytes that carry the thid mutation, the responsiveness to mitogenic stimulation was comparable to that of normal rat thymocytes. These results suggest that a defect in responsiveness to mitogenic stimulation in LEC rat thymocytes is controlled by multiple genetic loci and the thid locus is one of the important loci for the development of this abnormal phenotype.