The primary objective of HVAC systems is to make human occupants thermally comfortable. In practice, many systems fail to achieve this goal for a variety of reasons. Two important reasons are: improper system control objective and incapacity to deal with a nonuniform thermal environment. In this study, a new control objective is proposed based on the physiological load on the human thermoregulatory system. A closed-loop control algorithm is then developed using real-time human physiological signals. Experimental results on a thermal mannequin have shown that such a control algorithm is a better way to regulate the local thermal environment than traditional control algorithms. Instrumentation issues also are addressed in the paper.