Local human response to the non-uniform warm and humid thermal condition in a crowded building enclosure is investigated through numerical simulation in this paper. Mechanical ventilation under tropical weather condition is considered. A modified 25-node model of human thermoregulation is used to predict human thermal response in physiological parameters, such as body temperature and body heat loss. A three-dimensional field model for the thermal environment is coupled to the body model so that the non-uniform thermal condition in the ventilated environment can be simulated numerically and the individual responses at different locations can be evaluated. Under the specified ventilation condition, 0.4°C variation in the mean body temperature and 0.8°C variation in the mean skin temperature were caused by non-uniform thermal conditions, and the maximum variation in the body sensible and evaporative heat loss were about 10W and 5W, respectively. The numerical analysis of the local human response is useful in human comfort study as well as in the performance evaluation of ventilation and air distribution system.