The present study evaluated the effect of smoking deprivation on a biobehavioral index of distress tolerance, breath-holding duration, among 43 adult smokers in a repeated measures test (Session 1=smoking-as-usual, Session 2=12-h smoking deprivation). We theorized that distress tolerance is a context-dependent individual difference variable whose expression varies prospectively, within-individuals, as a function of smoking context. As predicted, participants' breath-holding duration was significantly shorter during an experimental session that immediately followed a 12-h smoking deprivation period than during a smoking-as-usual session. Furthermore, we theorized that among individuals with a pre-existing diathesis (i.e., psychiatric symptoms), smoking deprivation may activate a vulnerability process that decreases capacity to tolerate distress; in the absence of this stressor, these psychiatrically vulnerable smokers may express variable levels of distress tolerance. As predicted, we observed that level of psychiatric symptoms was significantly negatively correlated with breath-holding duration during the smoking deprivation, but not the smoking-as-usual session. These data advance our understanding of smoking and distress tolerance and the context-dependent phenomenology of distress tolerance.