We have studied the functional and proliferative capacity of the T cells of systemic lupus erythematosus (SLE)-prone MRL and BXSB mice during aging. The study was performed in vivo, in the delayed-type hypersensitivity (DTH) assay, and in vitro, in the mixed lymphocyte reaction (MLR). Both assays showed depressed T cell responses in MRL/l and male BXSB mice at 4 to 5 and 9 to 10 months of age, respectively, when a significant proportion of the animals showed clear-cut disease. At younger ages, the proliferation-dependent DTH was not affected in MRL/l and male BXSB mice. This is in agreement with the reported primary B cell defect of male BXSB mice, but not with the reported early T cell abnormalities in MRL/l mice. A subnormal reactivity of the highly proliferating T helper cells or the existence of a T cell subset with normal DTH reactivity might account for the relatively long-lasting normal DTH reactivity in MRL/l mice.