OBJECTIVES: To compare the pain threshold (the minimum pressure inducing pain) and pain tolerance (the maximum tolerable pressure) of different regions of the residual limbs of amputees by the indentation method and to evaluate the interface pressure distribution and distortion of the skin surface on indentation by finite element (FE) analysis. DESIGN: Crossover trial. SETTING: Rehabilitation engineering center. PARTICIPANTS: Eight transtibial amputees for indentation test and 1 for FE analysis. INTERVENTIONS: The load applied to the residual limbs using a Pelite or polypropylene indenter attached to a force transducer was increased until subjects could no longer tolerate the load. An FE model was built to simulate the indentation process with the experimentally recorded pain threshold used to load the indenters against the soft tissues. MAIN OUTCOME MEASURES: Pain threshold and tolerance and interface pressure and distortion of soft tissues. RESULTS: The patellar tendon and distal end of the fibula were the best and the worst load-tolerant regions, respectively. Some regions with a thicker layer of soft tissue had lower pain thresholds and tolerance than those with a thinner tissue layer. There was a trend for pain threshold and tolerance to decrease with age. The FE model showed that the peak pressure at the skin surface was very close when both indenters were loaded against the soft tissue at pain threshold limit. CONCLUSIONS: Contrary to common beliefs, regions with a thicker layer of soft tissue did not have a higher load-tolerant ability than thin-skinned regions. Pain threshold and tolerance could be age dependent. The FE model suggests that pain is triggered when peak pressure is applied to the residual limb exceeding a certain limit.