The environmental man-made pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has profound and deleterious effects on the endocrine system, and the pituitary gland is among TCDD endocrine target organs. In the present study, we have investigated the effects of TCDD (1 pM, 0.1 nM and 1 nM) on the AtT-20 pituitary cell line. TCDD induces cell death, with morphological and biochemical changes indicating the occurrence of both apoptotic and necrotic cell death. Exposed cells exhibited apoptotic features including DNA condensation, activation of caspase-3 and exposure of phosphatidylserine (PS) on the outer plasma membrane. Concomitantly, cells with necrotic morphology such as cell swelling and plasma membrane damage were also present. The relative level of Fas ligand mRNA was increased after TCDD exposure, as well as Fas and Fas ligand protein levels detected by Western blotting and immunocytochemistry. Taken together, the results suggest that TCDD induces both necrosis and apoptosis in the pituitary AtT-20 cells and that the Fas/FasL system plays a critical role in inducing necrotic cell death rather than apoptosis (supported by the Swedish Research Council).