Effects of the deregulated c-fos gene product on IL-2 expression were studied in splenic T cells from c-fos transgenic (H2-c-fos) mice. IL-2 gene expression and IL-2 production by H2-c-fos T cells stimulated with immobilized anti-CD3 Abs were enhanced and prolonged as compared with those by control T cells. Activator protein-1 activity in nuclear extract from the H2-c-fos T cells was also higher than that from the control cells. There was no significant difference in the activity of other transcription factors including IL-2 kappa B, NFAT, and Oct-1, between the H2-c-fos and the control T cells. However, activity of a negative regulatory element binding factor (NRE-A) in the H2-c-fos T cells was much lower than that in the control cells. These results suggest that c-Fos/activator protein-1 is a major regulatory factor for IL-2 gene expression in splenic T cells activated through the TCR/CD3 complex.