The impact of nicotine on the central nervous system is, in an important sense, neuroregulatory, with cascading effects on physiological and biochemical function as well as on behavioral activity. Accordingly, the neurotransmitter and neuroendocrine effects of nicotine constitute a critical part of its biological action, which includes reinforcing as well as pathophysiological consequences. This review focuses on nicotine's effects on cholinergic and non-cholinergic nicotine receptors and on the responses of catecholamines, monoamines, hypophyseal hormones, and cortisol. The contribution of critical variables, such as timing and duration of neuroregulator release and the patterns that make up the total response, is still largely unknown, particularly with regard to the effects of environmental context, history of nicotine use, and mode of administration. The evidence suggests that by altering the bioavailability of the above-listed neuroregulators, nicotine serves as a pharmacological "coping response", providing immediate though temporary improvement in affect or performance in response to environmental demands. Much of what is known to date is based on studies involving the administration of agonists and antagonists under different environmental conditions. Newer technological approaches such as autoradiography and positron emission tomography show potential for determining the neuroregulatory patterns involved and specifying nicotine's locus of action relevant to its behavioral and physiological effects.