Desipramine (DMI), like many antidepressant drugs, inhibit the production of paradoxical sleep (PS). In the present experiment, we have investigated the relationships between brain level of DMI and PS inhibition. Groups of rats had their sleep monitored after 1, 2 or 4 mg/kg of DMI. In other animals, the brain concentration of DMI was assayed at various times after the same treatments. The results indicate that a critical threshold concentration of 300 ng/g DMI in the brain is necessary for complete PS inhibition. This stage reappears only when the DMI level falls below this value, and its production resumes at a normal rate, provided the DMI level reached initially was not largely in excess of the threshold concentration. The results are discussed with regard to the present knowledge of specific binding of tricyclics in brain and their "ex vivo" action on norepinephrine uptake resulting in enhancement of collateral inhibiton of noradrenergic cells.