Earlier research indicated that a 10-session mood management (MM) intervention was more effective than a 5-session standard intervention for smokers with a history of major depressive disorder (MDD). In a 2 x 2 factorial design, the present study compared MM intervention to a contact-equivalent health education intervention (HE) and 2 mg to 0 mg of nicotine gum for smokers with a history of MDD. Participants were 201 smokers, 22% with a history of MDD. Contrary to the earlier findings, the MM and HE interventions produced similar abstinence rates: 2 mg gum was no more effective than placebo. History-positive participants had a greater increase in mood disturbance after the quit attempt. Independent of depression diagnosis, increases in negative mood immediately after quitting predicted smoking. No treatment differences were found in trends over time for measures of mood, withdrawal symptoms, pleasant activities and events, self-efficacy, and optimism and pessimism. History-positive smokers may be best treated by interventions providing additional support and contact, independent of therapeutic content.