The locomotor response to nicotine was assessed four weeks following destruction of mesolimbic dopamine (DA) neurons in rats by infusion of 6-hydroxydopamine into the ventral tegmental area. Resulting depletions of nucleus accumbens (N.Acc.) DA of up to 100% of control concentrations did not block the acute locomotor response to nicotine (0.4 mg/kg, base, s.c.). Such depletions also did not prevent the progressive enhancement of nicotine's locomotor effects when injections were repeated daily for nine days. These results suggest that mesolimbic DA is not necessary for the elicitation of locomotor activation by nicotine.