We constructed two strains of transgenic mice that carry the cDNA of either human interleukin-2 (IL-2) or the L chain of its receptor under the control of the H-2Kd promoter. The IL-2 transgenic mice expressed human IL-2 mRNA in the thymus, spleen, bone marrow, lung, muscle, and skin. Human IL-2 protein was also detected in their sera. The IL-2 transgenic mice suffered from dermatitis and pneumonia. Immune responses of their spleen cells against antigens were significantly impaired whereas their spleen cells responded well to polyclonal lymphocyte activators, suggesting that constitutive expression of IL-2 might have affected the repertoire formation of T cells in the mice. The IL-2 receptor (IL-2R) transgenic mice were healthy. We crossed the IL-2 and IL-2R transgenic mice to yield hybrid mice expressing both the ligand and the receptor constitutively. The life span of the hybrid mice was remarkably shortened. In addition to several abnormalities found in the IL-2 transgenic mice, spleen cells of the hybrid mice showed the strong natural killer activity which was ascribed to a large number (18%) of Thy-1+/CD3-cells unique to their spleen.