The thermal performance of glazing components of buildings is evidently not superior to other opaque building components. Therefore, given the ever increasing interest in reducing the energy consumption of buildings, there is likewise a concerted effort to improve the performance of glazing units. The most common insulated glass glazing systems are double-glazed insulated glass units (IGUs) that consist of two glass panes and a rim seal. The quality of the rim seal generally defines the service life of the double-glazed IGU because the seals prevent moisture from penetrating the gaseous cavity of the IGU. It is sometimes reported in Japan that after construction some double-glazed IGUs installed in a building form haze in the IGU cavity due to condensation. Window frames generally protect rim seals from factors causing aging of IGUs, e.g., elevated temperatures, high levels of humidity, and ultraviolet radiation. Wind pressure acting on the IGU can cause the panes to move, however, and these movements can be a major aging factor for rim seals. In this paper a study is described in which a fundamental test method is employed to evaluate the fatigue of IGU rim seals arising from wind pressure acting on the IGU. A two-way fatigue test is proposed that takes wind profiles into account. A 2-m-high double-glazed IGU incorporating a conventional rim seal was subjected to a fatigue test of approximately 350 cycles; the test replicated the frequency of occurrence of wind pressures as those that occur annually in Japan and arise from wind speeds in excess of 5 m/s. The deflections induced by the wind pressures were those that occurred at the center of the IGU over a year when taking into account a range of wind pressures having recurrence intervals of 0.002-50 years; this was regarded as an annual fatigue load. The fatigue loads were then applied to the pane of the IGU test specimen, and the corresponding repeated movements occurred in the IGU rim seal. Experimental results show that the moisture permeance of the rim seal that had undergone the accumulated fatigue damage from testing increased by a factor of approximately six. Based on these results it becomes apparent that it is important to evaluate the change in moisture permeance due to fatigue driven by wind pressure fluctuations; this permits considering changing the design of the IGU rim seals to minimize the effects of wind-induced fatigue damage.