We report the effects of physiological stimuli on extracellular dopamine (DA) in the medial prefrontal cortex (PFC) of the rat determined on-line in dialysates obtained every 5.5 min. The detection limit for DA was 0.03-0.1 pg/5 microl injection using a conventional HPLC set-up. Basal levels in PFC were at the detection limit, therefore 3 microM nomifensine was included in the Ringer perfusion fluid, producing readily detectable DA levels of 0.9 pg/injection. Perfusion with 3 microM TTX for 30 min decreased DA within 11 min to 10% of control. The routine use of rapid sampling of extracellular DA was applied to study cortical DA release in relation to behaviour. Exposure to a novel environment for 5.5 min led to an increase to 135%. Presentation of a food pellet to food-deprived rats resulted in a rapid increase to 150% within 5.5 min, which lasted 30-40 min, which is 10-20 min more than the time spent eating. Handling the rat for 5.5 min increased DA in PFC within 5.5 min to 160% and in 11 min to 190% of control followed by a 25-min period of a 50% increase, probably reflecting increased arousal. The results suggest that emotional arousal is a common denominator of increased cortical DA release and that responses are graded depending on the intensity of the stimulus.