Production of interleukin (IL)-2 by T lymphocytes is one of the earliest events during immune response. A mutant mouse strain was generated by replacing the IL-2 gene with a cDNA encoding green fluorescent protein (GFP). In this model, GFP fluorescence is readily detectable upon T cell activation and is mostly coexpressed with IL-2 at the single cell level. Thus, individual activated T cells can express the IL-2 gene biallelically. Upon stimulation through the T cell antigen receptor, CD4⁺ cells separate into distinct GFP⁺ and GFP⁻ populations, both of which are capable of differentiating into either Th1 or Th2 effectors. These mice allow noninvasive detection of IL-2 production by single cells and analysis of the subsequent differentiative fate of these cells as an immune response develops.