This study evaluated the effects of two central nicotinic-cholinergic receptor agonists and an antagonist on performance accuracy of a rat, delayed stimulus discrimination task (DSDT). Rats were trained to discriminate between an auditory and visual stimulus by pressing a right or left lever. To diminish the rat's ability to use mediating spatial strategies to solve the task, computer automated, retractable doors separated the animal from the levers during delay intervals, thus reducing positioning at the lever. After stable baselines were achieved, rats were grouped and administered placebo (saline) and nicotine, lobeline or mecamylamine in a randomized dose series. Each group received two complete series of the selected compound on different occasions. Mecamylamine impaired DSDT accuracy in a dose-dependent manner while optimal doses of nicotine and lobeline significantly improved accuracy. Nicotine differed from lobeline in regard to its interaction with a dose of mecamylamine (1.0 mg/kg) that had not impaired DSDT accuracy. Combined administration of lobeline and mecamylamine was followed by a significantly increased level of DSDT accuracy that was similar to the improvement following administration of lobeline alone. In contrast, combined administration of nicotine and mecamylamine did not result in increased DSDT accuracy. Furthermore, lobeline administration similarly improved accuracy of trials associated with both the light and the tone, while nicotine improved accuracy of trials associated with the light to a much greater degree. These data suggest that the increases in DSDT accuracy associated with lobeline may be expressed through non-nicotinic mechanisms or a nicotinic receptor which is not blocked by mecamylamine.