DSP-4, a neurotoxin which produces a marked and long-lasting depletion of norepinephrine (NE) in the central nervous system, was given in a dose of 50 mg/kg by i.p. route to rats prepared for chronic sleep recordings. Light sleep was significantly increased and REM sleep decreased during the first 2 days following DSP-4. Thereafter, REM sleep showed a consistent increase which attained significance on days 5 and 6 postinjection, thus indicating a permissive role for NE on this behavioral state. We examined also whether pretreatment with DSP-4 would modify the effects of clonidine, yohimbine, methoxamine, or clenbuterol on sleep and wakefulness. The sensitivity to α2-agents, methoxamine, and clenbuterol was respectively slightly increased or unchanged, decreased, and clearly increased after DSP-4.