This paper examines findings on the neuroregulatory effects of nicotine in an effort to formulate a unified hypothesis that can explain the remarkable persistence of smoking behavior. Because nicotine alters the bioavailability of several behaviorally active neuroregulators, including acetylcholine, norepinephrine, dopamine, beta-endorphin, and vasopressin, we propose that nicotine is "used" by smokers to produce temporary improvements in performance or affect. Under this formulation, a potential large number of exteroceptive and interoceptive cues unrelated to the nicotine-dependence cycle may serve as discriminative stimuli for smoking, over and above smoking to terminate or avoid withdrawal. The rapid action of nicotine, and its diverse neuroregulatory effects, render it particularly effective as a "coping response" to the demands of daily living. Of special interest in this regard is a biphasic pattern of arousal/catecholaminergic activation followed by cholinergic blockade or beta-endorphin release. Apparently smokers can adjust nicotine intake to enhance these effects selectively, which may add considerably to the appeal of smoking.