Nicotine has been shown in numerous previous studies to significantly improve memory on the radial-arm maze, yet the critical mechanisms underlying this effect are not fully characterized. Nicotine stimulates the release of a number of neurotransmitters important for memory function including (gamma-aminobutyric acid) GABA. The importance of nicotinic-GABA interactions regarding memory is currently unknown. The purpose of the current study was to determine the interactive effects of nicotine and the GABA agonist baclofen on working memory function as measured by choice accuracy in the radial-arm maze. Female Sprague-Dawley rats trained to asymptotic performance levels on a win-shift eight-arm radial maze task were used for assessment of nicotine-baclofen interactions. Low doses of baclofen improved memory performance while higher doses impaired it. Nicotine, as seen before, improved memory performance. Nicotine also significantly reversed the higher dose baclofen-induced deficit. These data show the importance of both nicotinic and GABA systems in working memory function and the interactions between these two transmitter receptor systems. This not only provides information concerning the neural bases of cognitive performance, it also lends insight into new combination treatments for memory impairment.