Because negative mood is a characteristic of both tobacco withdrawal and menstrual discomfort, withdrawal may vary by menstrual cycle phase. Tobacco withdrawal, mood, and menstrual discomfort were assessed in premenopausal women who quit smoking during either the follicular (Days 1-14 postmenstrual onset; n = 41) or luteal (Day 15 or longer postmenstrual onset; n = 37) phase of the menstrual cycle and maintained biochemically verified smoking abstinence during the postquit week. Women quitting during the luteal phase reported significantly greater increases in tobacco withdrawal and self-reported depressive symptoms than women quitting during the follicular phase. These results indicate that selecting a quit-smoking day early in the follicular phase may attenuate withdrawal and negative affect in premenopausal female smokers.