A 5- to 10-fold decline was observed in the proliferative activity of T cells stimulated with anti-CD3 mAb between young and old mice. However, the number of CD3 molecules on the T cell surface was almost comparable between young and old T cells. The formation of the second messenger such as inositol triphosphate (IP3) and diacylglycerol (DAG) after mitogenic stimulation decreased in old T cells as compared with young ones. The activity of phospholipase C (PLC), which is responsible for the liberation of IP3 and DAG from phosphatidylinositol-4,5-bisphosphate (PIP2) was not different between young and old T cells. The content of PIP2 in the membrane was also comparable between young and old T cells. These findings have suggested that the age-related decline in the proliferative activity of T cells could be due to impairment of intracellular signal transduction, probably in the pathway somewhere between TCR and PLC.