Subjective thermal comfort plays a critical role in body temperature regulation since this represents the primary stimulus for behavioral thermoregulation. Although both core (Tc) and skin-surface (Tsk) temperatures are known afferent inputs to the thermoregulatory system, the relative contributions of Tc and Tsk to thermal comfort are unknown. We independently altered Tc and Tsk in human subjects while measuring thermal comfort, vasomotor changes, metabolic heat production, and systemic catecholaminergic responses. Multiple linear regression was used to determine the relative Tc/Tsk contribution to thermal comfort and the autonomic thermoregulatory responses, by using the ratio of regression coefficients for Tc and Tsk. The Tc/Tsk contribution ratio was relatively lower for thermal comfort (1:1) than for vasomotor changes (3:1; P = 0.008), metabolic heat production (3.6:1; P = 0.001), norepinephrine (1.8:1; P = 0.03), and epinephrine (3:1; P = 0.006) responses. Thus Tc and Tsk contribute about equally toward thermal comfort, whereas Tc predominates in regulation of the autonomic and metabolic responses.