Because it is considered economically favorable to build arrays with high system voltage by serially connecting photovoltaic (PV) modules, it is necessary to explore the potential long-term degradation mechanisms that the modules may incur under such electrical potential. We performed accelerated lifetime testing of multicrystalline silicon PV modules in 85°C/85% relative humidity (RH) and 45°C/30% RH while placing the active layer in either positive or negative 600 V bias with respect to the grounded module frame. A negative bias applied to the active layer leads to more rapid and catastrophic module power degradation compared to a positive bias. This negative bias degradation is associated with significant shunting of individual cells as indicated by electroluminescence, thermal imaging, and I-V curves. Mass spectroscopy results support ion migration as one of the causes. Electrolytic corrosion is seen occurring with the silicon nitride antireflective coating and silver gridlines, and there is ionic transport of metallization at the encapsulant interface observed with damp heat and applied bias. Leakage current and module degradation are found to be highly dependent on the module construction, with factors such as encapsulant and front glass resistivity affecting performance. Measured leakage currents range from about the same as those seen in published reports of modules deployed in Florida (USA) to about 100 times higher when undergoing environmental chamber testing.