This work describes and presents results from a new three-dimensional whole-body model of human thermoregulation. The model has been implemented using a version of the “Brooks Man” anatomical data set, consisting of cubic volume elements (voxels) measuring 0.2 cm/side. The model simulates thermoregulation through passive mechanisms (metabolism, blood flow, respiration, and transpiration) and active mechanisms (vasodilatation, vasoconstriction, sweating, and shivering). Compared with lumped or compartment models, a voxel model is capable of high spatial resolution and can capture a level of anatomical detail not achievable otherwise. A high spatial resolution model can predict detailed heating patterns from localized or nonuniform heating patterns, such as from some radio frequency sources. Exposures to warm and hot environments (ambient temperatures of ) were simulated with the current voxel model and with a recent compartment model. Results from the two models (core temperature, skin temperature, metabolic rate, and evaporative cooling rate) were compared with published experimental results obtained under similar conditions. Under the most severe environmental conditions considered (, 27% RH for 2 h), the voxel model predicted a rectal temperature increase of , compared with a core temperature increase of from the compartment model and an experimental mean rectal temperature increase of . Similar, good agreement was noted for other thermal variables and under other environmental conditions. Results suggest that the voxel model is capable of predicting temperature response (core temperature and skin temperature) to certain warm or hot environments, with accuracy comparable to that of a compartment model. In addition, the voxel model is able to predict internal tissue temperatures and surface temperatures, over time, with a level of specificity and spatial resolution not achievable with compartment models. The development of voxel models and related computational tools may be useful for thermal dosimetry applications involving mild temperature hyperthermia and for the assessment of safe exposure to certain nonionizing radiation sources.