Norepinephrine (NE) and serotonin (5HT) likely inhibit the generation of ponto-geniculo-occipital (PGO) waves. Either desipramine (DMI) or sertraline (SER:1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthyl amine) was administered in the cat for 2.5 weeks to probe noradrenergic and serotonergic mechanisms, respectively. Placebo days were compared with the first day of drug and with days that followed 2.5 weeks of drug (chronic). PGO rates during REM sleep and the preceding transition period were significantly decreased by either chronic DMI or SER. Cat PGO waves resemble waves that accompany alerting to intense or novel stimuli in wakefulness. Depressive disorders in humans have features of hyperarousal; PGO wave suppression by antidepressant drugs may relate to clinical antidepressant actions.