The effects of lesions of the substantia nigra (electrolytic 2 mA 10 sec, or 6-OHDA 2 or 8 micrograms) and of the midbrain raphé nuclei (electrolytic 2 X 1.0 mA 10 sec) at 7 days postlesion on striatal levels of beta-phenylethylamine, DA, DOPAC, HVA, 5-HT and 5-HIAA and on hypothalamic levels of beta-phenylethylamine, DA, NA, 5-HT and 5-HIAA were investigated. In the presence of deprenyl (2 mg kg-1 2 hr SC), both electrolytic and 6-OHDA-induced dopamine-depleting lesions of the nigra but not 5-HT-depleting lesions of the raphé nuclei resulted in a marked decrease in the accumulation of beta-phenylethylamine. The marked reduction in accumulation of striatal beta-phenylethylamine in response to lesions of the substantia nigra indicates that the intraneuronal compartment is a major site of striatal beta-phenylethylamine synthesis. An equivalent decrease (approximately 40%) in the accumulation of 5-HT was observed following electrolytic lesions of the substantia nigra or raphé nuclei after administration of L-5-HTP (200 mg kg-1 hr IP). As L-5-HTP at the dose employed in this study is taken up non-selectively by both DA- and 5-HT-containing neurones the loss of L-AAD following nigral and raphé lesions was apparently equivalent. These results indicate that depletion of beta-phenylethylamine may not be simply attributable to a general loss of L-AAD following lesions of monoamine-containing neurones and suggest either co-localisation of beta-phenylethylamine and DA or the existence of distinct beta-phenylethylamine-containing neurones.