The concept of physiological individual response specificity (IRS) was critically discussed. A review of empirical studies focused on IRS magnitude, stability, and personality correlates. Using difference scores, an average of 33% of the participants showed a significant IRS. IRS stability was found in only 15% of the participants. In some studies, IRS incidence was associated with neuroticism or stress coping styles. We suggest that the IRS concept should include not only purely constitutional but also situational and psychological determinants. Predictions from this revised biopsychological model were tested with a data set comprising 48 healthy male participants who completed six tasks, which were replicated three times in 1-week intervals. At Session 1, 21% of the participants displayed a significant IRS. IRS stability was found in only 8% of the participants. Participants with a significant IRS at Session 1 reported higher levels of fear (anger and happiness as covariates) and of pounding heart. Between-session IRS (trait-IRS) but not within-session IRS (state-IRS) was associated with trait anxiety.