Noncardiac chest pain occurs frequently in medical practice and is often difficult to treat. We conducted a randomized double-blind, placebo-controlled, 8-week trial of paroxetine in 50 patients with noncardiac chest pain. None of the patients met criteria for panic disorder or major depression. Paroxetine-treated patients showed greater (P < .05) improvements than placebo-treated patients on the Clinical Global Impressions (CGI) scale. Both paroxetine and placebo-treated patients improved to a similar extent on selfrated pain measures, although baseline differences limited the interpretation of this outcome variable. There were no differences on other outcome ratings. Treatment was well tolerated. These preliminary findings extend other data on the potential of selective serotonin reuptake inhibitors for the acute treatment of noncardiac chest pain. Some recommendations for future studies to definitively test this potential are presented.