Patients with diabetes mellitus and peripheral neuropathy are at high risk for plantar skin breakdown due to unnoticed plantar stresses during walking. The purpose of this study was to determine differences in stress variables (peak plantar pressure, peak pressure gradient, peak maximal subsurface shear stress, and depth of peak maximal subsurface shear stress) between the forefoot (where most ulcers occur) and the rear foot in subjects with and without diabetes mellitus, peripheral neuropathy, and a plantar ulcer measured during barefoot walking. Twenty-four subjects participated: 12 with diabetes mellitus, peripheral neuropathy, and a plantar ulcer (DM+PN group) and 12 with no history of diabetes mellitus or peripheral neuropathy (control group). The subjects (11 men, 13 women) had a mean age (+/-SD) of 54+/-8 years. Plantar pressures were measured during barefoot walking using a pressure platform. Stress variables were estimated at the forefoot and the rear foot for all subjects. All stress variables were higher (127%-871%) in the forefoot than in the rear foot, and the peak pressure gradient showed the greatest difference (538%-871%). All stress variables were higher in the forefoot in the DM+PN group compared with the control group (34%-85%), and the peak pressure gradient showed the greatest difference (85%). The depth (X+/-SD) of peak maximum subsurface shear stress in the forefoot in the DM+PN group was half that in the control group (3.8+/-2.0 versus 8.0+/-4.3 mm, respectively). : These results indicate that stresses are relatively higher and located closer to the skin surface in locations where skin breakdown is most likely to occur. These stress variables may have additional value in predicting skin injury over the traditionally measured peak plantar pressure, but prospective studies using these variables to predict ulcer risk are needed to test this hypothesis.