Oxidative stress has been shown to have a myriad of effects on cells. Treatment of cells with oxidants, such as hydrogen peroxide or agents that induce reactive oxygen intermediates, has been shown to induce many cellular signaling pathways and, in some cases, cell apoptosis. Many chemotherapeutic treatments used to induce cell death do so via the induction of oxygen radicals. It is thought that oxidative stress can create, or modify the strength of, protein-protein interactions in cells that do not typically occur, or are weaker, under normal redox conditions. In this chapter, I describe a method to measure the strength of protein-protein interactions that may be enhanced during oxidative stress using the yeast two-hybrid system.