The reinforcing properties of nicotine involve actions at nicotinic acetylcholine receptors located on dopamine (DA) neurons in the ventral tegmental area (VTA). The pedunculopontine tegmental nucleus (PPTg) is involved in the regulation of these DA neurons, and those of the substantia nigra pars compacta (SNc). The PPTg can be subdivided into anterior (aPPTg) and posterior (pPPTg) regions on the basis of its innervation of midbrain DA neurons – the pPPTg innervates both VTA and SNc while the aPPTg innervates SNc. As the reinforcing actions of nicotine depend on its actions in the VTA more than SNc, it was hypothesized that excitotoxic lesions of pPPTg would alter nicotine reinforcement, measured by intravenous self-administration, while lesions of aPPTg would not. Rats were given ibotenate lesions of pPPTg or aPPTg, followed by intravenous catheterization. Intravenous self-administration (IVSA) of nicotine (0.03 mg/kg/inf) was carried out until a stable response baseline was reached. A dose–response function for nicotine was then established. There was no significant effect of aPPTg lesions on nicotine IVSA, while IVSA was significantly elevated following pPPTg lesions, compared with both sham lesioned controls and aPPTg excitotoxin lesioned rats. This was found across all doses, including saline, of the dose–response function. The differential effect of aPPTg lesions and pPPTg lesions suggests that disruption of regulatory innervation from pPPTg results in altered regulation of VTA DA neurons. The resulting change in nicotine self-administration behaviour was hypothesized to reflect either a reduction in intrinsic nicotine reward value, or enhancement of associative incentive salience.