Amphetamine and various amphetamine derivatives, phenmetrazinc, pipradrol, methylphenidate and HCA can increase the concentration of 5-HIAA in the rat brain without changing that of 5-HT. Metamphetamine produced a de- crease in 5-HT and no effect on 5-HIAA whereas 10-hydroxyamphetamine produced no effects on 5-HT and 5-ttIAA. The experiments performed at different environ- mental temperatures (12--14~ 21--22~ and 21--28~ with simultaneous measurements of the body temperature indicate that no simple correlation exists between the drug induced hyperthermia and the effect on 5-HIAA. The amphet- amine and phenmetrazine effect on 5-HIAA seems to be related to hyperthermia whereas the pipradrol and methylphenidate effect on 5-HI_AA appears independent of hyperthermia. Apomorphine (2 2.5 mg/kg) which activates central dopamine receptors produced a significant increase in 5-H~AA whereas clonidine (0.5 mg/kg) which activates central noradrenaline receptors produced a significant decrease in 5-HIAA. In conclusion, the effect of various amphetamines on 5-HT metabolism seems very complex in mechanism of action and might be related to hyperthermia, to a direct effect on 5-tIT neurons and to the ratio between central dopamine/nor- adrenaline receptor activation of these drugs.