In the present study, we investigated the different types of neocortical rhythmic slow activity (RSA) during wakefulness and paradoxical sleep as well as their pharmacological modification. During wakefulness, the high-frequency (7–9 Hz) RSA1 type, which is atropine-resistant, is accentuated by forebrain stimulation and is abolished by urethane, clonidine and alcuronium. These drugs induce the low-frequency (4–6 Hz) RSA2 type that is atropine-sensitive and is activated by cholinergic agents and by some drugs such as tabernanthine, ibogaine, vincamine, SL 76.188-MS (10-chloro-hexahydrocanthinone methanesulphonate). The effects of pilocarpine and SL 76.188-MS on RSA2 are antagonized by atropine and hemicholinium-3, which suggests the involvement of a cholinergic pathway in the neocortical RSA activation (as has been demonstrated for the hippocampal RSA). During paradoxical sleep, two types of RSA are also observed: RSAT, of low frequency (5–7 Hz) present during its tonic components, and RSAP, of high frequency (7–9 Hz) which is well correlated with phasic phenomena such as bursts of rapid eye movements generated, or controlled, by cholinergic mechanisms. Imipramine reduces phasic phenomena and the periods of neocortical RSAP. Alcuronium does not modify RSAP in paradoxical sleep-deprived rats and suppress RSA1 during arousal, observations which would suggest that RSAP and RSA1 are regulated by two distinct central mechanisms. The EEG studies of neocortical RSA during wakefulness and paradoxical sleep allow the selection and the differentiation of pharmacological agents. Furthermore, this approach not only may represent a basis for the treatment of deficits in the regulation of vigilance and memory, but also a novel strategy for the analysis of RSA type of paradoxical sleep with respect to antidepressant and anxiolytic tr