Background: Studies suggest that peroxynitrite (ONOO-), formed from superoxide and nitric oxide (NO) is a mediator of oxidant-induced cellular injury. Hypothesis: 3 morpholinosydnonimine (SIN-1), which releases superoxide and NO simultaneously will increase calcium oscillation in synaptosomes and hypothermia will inhibit this phenomenon. Subjects: 58 days guinea pig fetuses. Method: Cortical synaptosomes were prepared from fetal brain tissue, loaded with Fura-2/AM and divided into 3 groups Two groups were incubated at pH 7.4, 37 °C for 1 hr, with (S37 or without (C37) SIN-1 (100 μM). A third group, treated with SIN-1 was incubated at 27 °C (S27. Intrasynaptosomal calcium ([Ca2+]i) was measured fluorometrically. Synaptosomal viability was documented by measuring mitochondria activity (MTT reduction). Results: Mitochondria activity was not affected by SIN-1. The Ca2+ increase in C37, S37 and S27 was 419 ± 113, 1453 ± 133 and 647 ± 239 pM/sec, respectively. The calcium oscillation was higher in S37 vs C37(p<0.001), and was significantly inhibited in S27 vs S37(p<0.01). Conclusion: The results suggest that SIN-1, via ONOO- production, modifies the calcium permeability of synaptosomal membrane, including calcium ion channels such as NMDA receptor, and results in an increased [Ca2+]i. This mechanism is temperature dependent. We speculate that ONOO -mediated increasing Ca2+ will lead to stimulation of phospholipase A2 and NO synthase, which further initiate ONOO production (Funded by NIH-HD-20337)