Sleep, waking, and EEG power spectra were investigated in rats with spinal 5,6-dihydroxytryptamine (5,6-DHT) lesions, following 20 mg/kg zimeldine or vehicle IP injections. 5,6-DHT selectively lesioned the descending serotonergic pathways. Lesion alone did not change sleep and waking stages compared to baseline, except for a reduction in REM sleep. Consistent with earlier findings, zimeldine in nonlesioned rats increased waking the first 2 h of recording. Zimeldine treatment in lesioned rats gave a significant additional 50% increase in waking the first 2 h and a corresponding decrease in total slow wave sleep, suggesting a potentiation of these effects. Zimeldine gave no significant changes in waking EEG power spectral density. Lesion gave a tendency to reduction between 4.0 and 15.5 Hz compared with baseline, and between 10.0 and 16.5 compared to the independent control group. In both comparisons, the combined treatment strengthened this effect, again suggesting a potentiating effect of lesion. In sleep, zimeldine reduced power over the whole spectrum (0.5-20.0 Hz), less in the lower frequencies than in the higher frequencies.