CD45 is a leukocyte specific protein tyrosine phosphatase and is a major lymphocyte cell surface glycoprotein ( see refs. 1 – 3 for reviews). CD45 has been shown to be important for the transmission of signals by the T and B cell antigen receptors during both development and antigen induced activation. The phosphatase activity of CD45 has been shown to be required for efficient signaling by the T-cell receptor complex, yet little is known of how or whether the phosphatase activity of CD45 is regulated. In this chapter, we describe a simple and sensitive method to measure the phosphatase activity of CD45 isolated directly from T cells. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.