Preliminary animal research suggests that yohimbine hydrochloride, a selective competitive alpha2-adrenergic receptor antagonist, accelerates fear extinction and converts ineffective extinction regimens (long intertrial intervals) to effective ones. This randomized placebo controlled study examined the potential exposure enhancing effect of yohimbine hydrochloride in claustrophobic humans. Participants (71% undergraduate students and 29% community volunteers) displaying marked claustrophobic fear (n = 24) were treated with 2 1-h in vivo exposure sessions. Participants were randomly allocated to take 10.8 mg yohimbine hydrochloride (n = 12) or placebo (n = 12) prior to each exposure session. Outcome measures included peak fear during a behavioral avoidance task, the Claustrophobia Questionnaire, and the Claustrophobic Concerns Questionnaire. Results showed that both conditions improved significantly at post-treatment with no significant difference between groups. Consistent with prediction the group that took yohimbine hydrochloride prior to exposure sessions showed significantly greater improvement in peak fear at the one-week follow-up behavioral assessment (d = 1.68). This was also true across other outcome measures with large to very large effect sizes. These data provide initial support for exposure enhancing effect of single-dose yohimbine hydrochloride in a clinical application.