A test apparatus was developed to investigate the effects of mechanical stress application on collagen remodeling in skin. The system maintained a 4.5-cm x 5.5-cm skin explant at an air interface with controlled temperature, relative humidity (RH), and carbon dioxide concentration [CO2] while allowing controlled compressive and shear forces to be applied to the skin surface. For environmental control, a custom-designed flow system under Proportional-Integral-Derivative (PID) control was used. Evaluation tests demonstrated that the system maintained air above the explant at a temperature within 1 degrees C of the 37.5 degrees C set point, RH within 5% of the user-specified set point (range of 5% to 95%), and [CO2] within 1% of the 5% [CO2] set point. Least-squares errors in cyclic compressive and shear forces (0- to 20-Hz bandwidth) delivered to the explant were 0.9% and 2.8%, respectively, of user-specified values. Pig skin samples cyclically stressed for 1 hr/day for 3 days with either compressive force only or a combined compressive and shear force had significantly smaller collagen fibril densities compared with an unstressed control, a result consistent with in vivo test data. Collagen fibril diameters were significantly larger for stressed versus control for some of the samples, but the changes were not as substantial as from in vivo testing. This result may have been due to the shorter study duration in vitro (3 d versus 20 d in vivo). The system allows insight into the mechanisms of skin adaptation to mechanical stress to be investigated on a cellular and molecular level, potentially leading to therapies to encourage adaptation in at-risk patients.