An analysis of the analgesic activity of the endogenous brain amines, phenylethylamine (PEA) and phenylethanolamine (OHPEA), was carried out in mice using the hot-plate and tail-dip tests. PEA (10 mg/kg) and OHPEA (10 mg/kg) had an analgesic effect in mice pretreated with pargyline (100 mg/kg/24 h). FLA-63 (50 mg/kg/3 h) prevented the analgesic effect of PEA and potentiated that of OHPEA in mice pretreated with pargyline. Reserpine (10 mg/kg/24 h) prevented the analgesic effects of PEA and OHPEA in pargyline pretreated mice. PCPA prevented the analgesic actions of OHPEA in mice pretreated with both pargyline and FLA-63. These data suggest that the analgesic effect of PEA was mediated through a β-hydroxylated amine, possibly OHPEA, and that the analgesic effect of OHPEA may involve serotonergic neurons.