Prolonged periods of driving in monotonous situations may lower a driver's activation state as well as increasing their stress level due to the compulsion to maintain safe driving, which may result in an increased risk of a traffic accident. There is therefore an opportunity for technological assessment of driver physiological status to be applied in-car, hopefully reducing the incidence of potentially dangerous situations. As part of our long-term aim to develop such a system, we describe here the investigation of differential skin temperature measurement as a possible marker of a driver's stress level. 10 healthy male subjects were studied, under environment-controlled conditions, whilst being subjected to simulated monotonous travel at constant speed on a test-course. We acquired measurements of relevant physiological variables, including truncal and peripheral skin temperatures (Ts), beat-by-beat blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR), and normalized pulse volume (NPV) used as an indicator of local peripheral vascular tone. We then investigated the driver's reactivity in terms of cardiovascular haemodynamics and skin temperatures. We found that the simulated monotonous driving produced a gradual drop in peripheral Ts following the driving stress, which, through interpretation of the TPR and NPV recordings, could be explained by peripheral sympathetic activation. On the other hand, the truncal Ts was not influenced by the stress. These findings lead us to suggest that truncal-peripheral differential Ts might be used as a possible index indicative of the driver's stress. Such an index, if decisively validated, would be easy to apply in real driving situations by using radiation thermometer.