This and the following two papers examine the activity of locus coeruleus noradrenergic (LC-NE) neurons in response to a variety of physiological manipulations in unanesthetized, unrestrained cats. Unit responses were studied during a constant behavioral state in order to avoid the potentially confounding effects of state changes upon LC-NE unit discharge. In the present study, LC-NE unit activity was recorded during two thermoregulatory challenges: ambient heating and pyrogen-induced fever. These two conditions are particularly interesting since the direction of body temperature change that they produce is the same, but the thermoregulatory responses elicited are opposite, i.e. heat loss and heat gain. LC-NE neurons were activated by both manipulations. In response to ambient heating, neuronal activity increased only with the occurrence of panting, and not during earlier portions of the heating session. Following pyrogen administration, LC-NE neurons responded only during the peak increase in body temperature. Both of these effects on unit activity occurred independent of changes in behavioral state. Since both manipulations similarly increased LC-NE unit activity, despite eliciting opposite thermoregulatory responses, it appears that these neurons do not play a specific role in thermoregulation, but may participate in the response to physiological challenges in general.