This study investigated whether taking medications for transdermal hormone replacement therapy (HRT) influenced smoking-cessation variables in postmenopausal women undergoing short-term abstinence from cigarettes. Women were recruited into two groups according to their pre-enrollment medication status - those currently on HRT (n=17) or those not on HRT (n=13). The HRT group had their previous medication replaced with a standard 0.1 mg estradiol transdermal system and 2.5 mg of Cycrin daily. After 2 weeks of medication adjustment, participants continued smoking as usual for 1 week, at which time baseline measurements were taken. Participants were then instructed to quit smoking for the remaining 2 weeks. They were provided with smoking-cessation counseling and monitored for abstinence. Data were collected during five clinic visits on all dependent measures: Minnesota Nicotine Withdrawal Scale, Beck Depression Inventory (BDI) scale, Profile of Mood States, Motor Speed Tasks, and Reaction Time Test. Contrary to our hypothesis, the exogenous hormone use did not have a differential effect on most of the dependent variables during the first 2 weeks of smoking abstinence. One exception was depressive symptomatology: the BDI change scores (week 2 - baseline) differed significantly for the HRT and non-HRT groups (p=.045), with women in the HRT group experiencing an increase in depressive symptomatology. This finding, though preliminary, may have clinical implications for postmenopausal women who attempt to quit smoking while on HRT, particularly since depressed mood following abstinence is associated with a relapse to smoking.