Beneficial effects have been observed in University of Washington Pain Clinic patients treated with tricyclic antidepressants, but such effects occur much earlier than predicted mood elevation. A laboratory investigation of pain perception was employed to test the hypothesis that doxepin, a tricyclic antidepressant, has analgesic properties. Healthy, normal volunteers were tested over a 4-week period during which they repeatedly performed Sensory Decision Theory tasks while undergoing painful dental stimulation. Doxepin and a placebo were administered after baseline measurement for 4 weeks under double blind conditions. No significant changes due to drug administration were observed in detection threshold or sensory sensitivity indices, but response bias against reporting the stimuli as painful changed dramatically after subjects began ingesting capsules. This effect was evident in both drug and placebo groups, and it was maintained across repeated weeks of testing. These observations suggest that the instructions given patients when the drug is administered have a profound effect on pain report.