The purpose of this study was to investigate the influence of the pedunculopontine nucleus (PPN) on the electrical activity of entopeduncular nucleus (EP) in the rat and to analyze the influence of the subthalamic nucleus (STN) on the PPN-evoked responses of EP cells. Most of the EP neurons recorded (65.1%) were identified electrophysiologically as output cells projecting to the lateral habenula while only a minority (3.8%) were output cells to the PPN. Stimulation of the PPN in intact rats caused a short-latency (2.5 +/- 2.0, S.D. ms) activation in 22.6% and suppression of activity in 8.5% of EP neurons recorded. The mean impulse rate of EP neurons in intact rats was 27.0 +/- 5.5, S.D. imp./s and the overall mean interspike interval 36.8 +/- 7.1, S.D. ms. In rats where the PPN had been destroyed 10-12 days before recording by a local microinjection of kainic acid only a few EP neurons were still responsive to stimulation of the PPN showing suppression of activity. In these rats the kainate lesion slowed the impulse spontaneous activity to 14.3 +/- 6.3, S.D. imp./s and markedly altered the distribution of interspike intervals in 62.5% of the EP neurons recorded. The overall mean interspike interval in this group of deregulated neurons was 68.2 +/- 20.1, S.D. ms. A small kainate lesion of the STN placed 4-5 days before recording, on the other hand, did not affect the spontaneous activity of EP cells but increased the percentage of cells which were activated (43.6%) by stimulating the PPN. The present data demonstrate a predominant activatory influence of the PPN on EP cells and suggest that destruction of the STN may affect the responsiveness of entopeduncular cells to stimulation of the PPN possibly through the removal of a tonic inhibitory STN influence on the EP.