X-linked lymphoproliferative disease (XLP) is a rare inherited immunodeficiency most commonly caused by deficiency in the protein SAP. Following infection with the common virus that causes infectious mononucleosis (also known as mono or glandular fever), boys with XLP often develop an extreme, usually fatal, accumulation of activated immune cells known as cytotoxic T lymphocytes; but the mechanistic link between this and SAP deficiency has not been determined. However, Michael Lenardo and colleagues, at the NIH, Bethesda, have now found that T cells from individuals with XLP are resistant to cell death triggered by repeated stimulation of a cell surface protein complex known as the TCR. As repeated TCR stimulation normally constrains T cell expansion during immune responses, the authors propose that this makes the T cells susceptible to uncontrolled expansion upon infection.