The aim of the present study was to investigate changes in the firing activity of thalamic parafascicular nucleus (PF) neurons at different time periods after 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc) and the role of the pedunculopontine nucleus (PPN) in these changes. In normal rats, the firing rate of PF neurons was 3.66+/-0.37 spikes/s. In rats with 6-OHDA lesions of the SNc, the firing rate of PF neurons slightly decreased to 3.19+/-0.35 spikes/s during the third week compared to normal rats, unexpectedly, as moving on to fifth week, the firing rate increased significantly to 4.82+/-0.31 spikes/s. In rats with ibotenic acid lesions of the PPN, the firing rate decreased significantly to 1.98+/-0.19 spikes/s compared to normal rats. When the SNc and PPN were double lesioned, the firing rate of PF neurons decreased significantly to 2.36+/-0.23 spikes/s during the third week and 2.16+/-0.16 spikes/s during the fifth week post-lesions. The separate lesions of the PPN, SNc, and double lesion of both in the rats did not change the firing pattern of PF neurons compared to normal rats. These findings demonstrate that PF neurons are hyperactive in the 6-OHDA-lesioned rats suggesting the implication of this nucleus in the pathophysiology of parkinsonism. Furthermore, the fact that the PPN lesions induced a decrease in the firing rate of PF neurons in normal and SNc-lesioned rats suggests that the PF is under major control of the PPN.