A common but potentially severe malady afflicting permanent wheelchair users is pressure sores caused by elevated soft tissue strains and stresses over a critical prolonged period of time. Presently, there is paucity of information regarding deep soft tissue strains and stresses in the buttocks of humans during sitting. Strain and stress distributions in deep muscle and fat tissues were therefore calculated in six healthy subjects during sitting, in a double-donut Open-MR system, using a "reverse engineering" approach. Specifically, finite element (FE) models of the undeformed buttock were built for each subject using MR images taken at the coronal plane in a non-weight-bearing sitting posture. Using a second MR image taken from each subject during weight-bearing sitting we characterized the ischial tuberosity sagging toward the sitting surface in weight-bearing, and used these data as displacement boundary conditions for the FE models. These subject-specific FE analyses showed that maximal tissue strains and stresses occur in the gluteal muscles, not in fat or at the skin near the body-seat interface. Peak principal compressive strain and stress in the gluteus muscle were 74+/-7% and 32+/-9 kPa (mean+/-standard deviation), respectively. Peak principal compressive strain and stress in enveloping fat tissue were 46+/-7% and 18+/-4 kPa, respectively. Models were validated by comparing measured peak interface pressures under the ischial tuberosities (17+/-4 kPa) with those calculated by means of FE (18+/-3 kPa), for each subject. This is the first study to quantify sub-dermal tissue strain and stress distributions in sitting humans, in vivo. These data are essential for understanding the aetiology of pressure sores, particularly those that were recently termed "deep tissue injury" at the US National Pressure Ulcer Advisory Panel (NPUAP) 2005 Consensus Conference.