The trichothecene mycotoxin T-2 is reported to exhibit immunotoxic activity. The potential presence of T-2 in foods renders it as public health hazard and its toxicity needs to be better understood. We investigated the in vitro effects of T-2 at sub-toxic (0.1 ng/ml) and toxic (10 ng/ml) levels on freshly isolated human peripheral blood lymphocytes (PBLs). We observed no direct influence on untreated PBLs. The toxic dose of T-2, however, totally inhibited phytohemagglutinin-induced T lymphocyte proliferation and caused early apoptosis that peaked after 8h of exposure. Both major T lymphocyte subsets (CD4+ and CD8+) were affected as they appeared to show a positive response to T-2 at 8h followed by their sharp reduction after 96 h. Further investigation on the naïve (CD45RA+) and memory (CD45RO+) subpopulations confirmed these observations and indicated that T-2 affected equally all the subpopulations studied, although PHA preferentially stimulated CD45RO+ T lymphocytes. Sub-toxic T-2 appeared to exhibit co stimulatory properties to PHA-stimulated cells. These results support the hypothesis that T-2 affects the activation-induced cell death mechanism of T lymphocytes.