Peroxynitrite (0.5–50 μM) induced dose-dependent cytotoxic effects in rat pancreatic acinar AR4–2J cells. Glutathione (2 mM) and ebselen (10 μM) partially reduced the cytotoxicity caused by 1–10 μM concentrations of peroxynitrite. Higher concentrations (10–50 μM) of peroxynitrite induced DNA smear suggestive of necrosis, while lower concentrations (2–5 μM) induced DNA fragmentations suggestive of apoptosis. The effects of peroxynitrite on [Ca2+]ishowed a similar dose dependency. Peroxynitrite concentrations >10 μM rapidly increased [Ca2+]i in a dose-dependent manner, while concentrations <5 μM did not affect [Ca2+]i. In contrast, the presentation of wild-type P53 was accelerated at lower concentrations of peroxynitrite (≤10 μM) but not at higher concentrations (50 μM). The present study suggests that peroxynitrite at lower concentrations (2–5 μM) induces wild-type P53 and apoptosis, which is potentially a protective response toward the DNA damage caused by peroxynitrite. On the other hand, higher concentrations of peroxynitrite (10–50 μM) rapidly increase [Ca2+]i and eventually induce necrosis.