The effects of p-chlorophenylalanine ( p-CPA), α-methylparatyrosine (α-MPT), α-methylmetatyrosine (α-MMT), α-methyl DOPA (α-MDOPA) and disulfiram have been studied on the hyperirritability syndrome of septal rats. p-CPA, in doses of 300 mg/kg, produces immediate taming of septal animals. Administration of p-CPA prior to the septal destruction, in doses of 300 and 600 mg/kg, does not influence the appearance or the duration of the hyperirritability syndrome. α-MPT, in doses of 100–200 mg/kg, causes in septal rats a behavioral depression up to a lethargic state and a lowering of the irritability scores. Injected before septum destruction, α-MPT induces only a mild sedation and does not hinder the development of the septal syndrome. No effect is observed when α-MMT or α-MDOPA are administered to septal rats for two consecutive days in doses of 200 mg/kg, twice a day. Disulfiram, in doses of 200 and 400 mg/kg, was also ineffective. These results are discussed in relation to the effect of these drugs on the content of indol- and catechol-amines in the brain.