In contrast to previous stress research, studies concerning phobic disorders have never systematically investigated individual response differences between phobic participants integrating numerous different response measures. The aim of this article is to clarify the existence of significant individual response differences in psychophysiological responses (e.g., heart rate, skin conductance responses (SCR), corrugator, cortisol), subjective ratings (e.g., valence, arousal), and avoidance behavior in 46 spider phobic and 44 non-phobic women when exposed to 20 phobic and 20 neutral pictures. Previous studies that did not attend to individual response differences showed that, during phobic stimulation, phobic individuals have increased psychophysiological responses (heart rate, SCR, and corrugator responses), more negative valence rating, and more subjective arousal than non-phobic individuals. These results were confirmed by our data. With regard to individual response uniqueness, 1/3-2/3 of spider-phobic women with low responsiveness in heart rate, cortisol, and avoidance behavior were indistinguishable from non-phobic women during phobic stimulation. With SCR, corrugator EMG, and subjective ratings, no individual response uniqueness was found. Based on the findings, exposure therapy might be improved by tailoring interventions to individuals with a therapeutic focus on those psychophysiological measures that show the highest individual responsivity.