The aim of this study was to analyze whether immunosuppressants could affect NO-induced thymocytes apoptosis. S-Nitroso-N-acetyl-D,L-penicillamine (SNAP, an NO donor) has an apoptotic effect on murine thymocytes. This NO-induced thymocyte apoptosis is associated with a reduced uptake of DiOC(6), a fluorochrome which incorporates into cells depending on their mitochondrial membrane potential (DeltaPsi(m)). The immunosuppressant, cyclosporin A, partially inhibited NO-induced thymocyte apoptosis as well as the reduction of DeltaPsi(m). In contrast, another immunosuppressant, FK506, did not affect NO-induced thymocyte apoptosis. Although FK506 and cyclosporin A inhibit T-cell signal transduction by the same mechanism, their effects on mitochondria may contribute to the differential apoptosis induction ability.