Clomipramine is a serotonin reuptake blocker which produces an increased rate of firing in lateral septal neurons of the rat. However, it is unknown whether the response of dorsal raphe nucleus stimulation on the firing rate of the lateral septal neurons is modified by clomipramine treatment. Two programs of stimulation were employed. In the first, iterative stimulation (0.3 Hz, 1 ms, 0.1 mA) produced a complex pattern of response in which activation responses predominated, and clomipramine increased the duration and the firing rate of afterdischarge. In the second program a short train of pulses (300 Hz, 500 ms, 0.1 ms) was applied to the dorsal raphe nucleus. Clomipramine increased both the duration and the frequency of firing with respect to the saline-treated group. The present data show that dorsal raphe nucleus stimulation produces a long-lasting increase in the firing rate of lateral septal neurons which is enhanced by clomipramine. Since clomipramine applied to the septal area produces a decrease in firing, it is concluded that actions taken by clomipramine on raphe nuclei produce a disinhibitory process in the lateral septal neurons.