The synergistic effect of perazine and hexobarbital was studied by interference with drugs which alter the adrenergic, serotonergic and cholinergic systems. The determination of hexobarbital level in blood and brain was used as an indication of the rate of its biotransformation. According to the findings perazine, dihydroergotamine (DHE), and phentolamine (in low doses) as well as an elevation of dopamine level prolong the anaesthesia by way of a central mechanism. Phentolamine (in higher doses) and the anticholinergic drug biperidin slow down the metabolism of hexobarbital, probably by inhibiting the hepatic microsomal enzymes. An alteration of the overall level of catecholamines, serotonin and acetylcholine had no effect on the hexobarbital-induced anaesthesia. The mild hyperthermia caused by all drugs tested, did not influence the duration of hexobarbital sleeping time. The possibility that perazine, like other α-receptor blocking agents, causes a preponderance of inhibitory dopaminergic neurons by obstructing the excitatory norepinephrine receptors in the central nervous system is discussed. This effect might also occur if the dopamin level in the brain is increased.