Extensive research on the hypothalamic-pituitary-adrenal (HPA) axis response to stress has not clarified whether that axis is activated by phobic anxiety. We addressed this issue by measuring cortisol in situational phobics during exposure treatment. Salivary cortisol was measured in 11 driving phobics before and during three exposure sessions involving driving on crowded limited-access highways and compared with levels measured in 13 healthy controls before and during two sessions of driving on the same highways. For each subject, data collected in the same time period on a comparison nondriving day served as an individual baseline from which cortisol response scores were calculated. Cortisol levels of driving phobics and controls did not differ on the comparison day. Phobics also had normal cortisol response scores on awakening on the mornings of the exposures but these were already increased 1 hour before coming to the treatment sessions. Phobics had significantly greater cortisol response scores during driving exposure and during quiet sitting periods before and afterward. These greater responses generally paralleled increases in self-reported anxiety. At the first exposure session, effect sizes for differences in cortisol response scores between the two groups were large. Initial exposure to driving in the first session evoked the largest responses. The data demonstrate that the HPA axis can be strongly activated by exposure to, and anticipation of, a phobic situation.