A mathematical model for predicting human thermal and regulatory responses in cold, cool, neutral, warm, and hot environments has been developed and validated. The multi-segmental passive system, which models the dynamic heat transport within the body and the heat exchange between body parts and the environment, is discussed elsewhere. This paper is concerned with the development of the active system, which simulates the regulatory responses of shivering, sweating, and peripheral vasomotion of unacclimatised subjects. Following a comprehensive literature review, 26 independent experiments were selected that were designed to provoke each of these responses in different circumstances. Regression analysis revealed that skin and head core temperature affect regulatory responses in a non-linear fashion. A further signal, i.e. the rate of change of the mean skin temperature weighted by the skin temperature error signal, was identified as governing the dynamics of thermoregulatory processes in the cold. Verification and validation work was carried out using experimental data obtained from 90 exposures covering a range of steady and transient ambient temperatures between 5°C and 50°C and exercise intensities between 46 W/m² and 600 W/m². Good general agreement with measured data was obtained for regulatory responses, internal temperatures, and the mean and local skin temperatures of unacclimatised humans for the whole spectrum of climatic conditions and for different activity levels.