Nicotine, the presumed active pharmacological agent in tobacco, produces variable effects on behavior that are at best described as "paradoxical" in nature. Thus, nicotine, via tobacco use in humans or nicotine administration in experimental animals, tends to transpose behavior depending on predrug baseline rates of behavior. High rates of behavior appear to be reduced, while low rates of behavior appear to be increased by nicotine. This work further proposes that nicotine's variable effects on behavior may be related to its capacity to act as a behavioral agonist and/or antagonist via its ability either to activate or to desensitize distinct central nicotinic acetylcholinergic receptors (nAChR's). Nicotine is portrayed as a neuronal modulating agent that can affect behavior contingent upon the genetic makeup of the individual subject being studied. Depending on the structure, function, and location of distinct nAChR's, nicotine appears to be able to induce a wide range of behavioral effects important to the tobacco user. However, this does not rule out the role the importance that other biogenic amine systems (i.e., serotonin or dopamine) may have in the genetics of tobacco use or nicotine's variable effects on behavior.