Most drugs of abuse enhance mesolimbic dopaminergic transmission and locomotor activity in laboratory animals and, when given repeatedly, further increase these measures, a phenomenon termed sensitization. Sensitization-related neuroadaptations have been proposed to be important in the development and maintenance of addiction. It has been suggested that both ethanol and nicotine interfere with central nicotinic acetylcholine receptors located on brain dopamine neurons, a mechanism of action that may provide a basis for the often observed co-administration of these drugs of abuse. In this study we investigated the effects of a challenge with ethanol (2.5g/kg, i.p.) or nicotine (0.2mg/kg, s.c.) on locomotor activity and monoamine turnover in mice subchronically pretreated with nicotine. Nicotine pretreatment significantly enhanced the ethanol-induced locomotor stimulation and elevation of dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) quotient in the brain. These results suggest that neuronal mechanisms related to the locomotor stimulatory effects of ethanol may be sensitized by preexposure to nicotine.