The effect of direct intrathecal injection ofp‐chloroamphetamine (PCA) into the lumbar subarachnoid space was investigated in mice. PCA (0.6–20 μg) induced a dose‐related prolongation of response latencies in the tail‐flick test, but failed to affect the hind‐paw lick response in a hot‐plate test employing slowly rising temperature. PCA (5μg)given intracerebroventricularly did, however, significantly elevate the response temperature in the hot‐plate test. The antinociceptive effect of PCA in the tail‐flick test was prevented by spinalization, by pretreatment with the selective serotonergic re‐uptake blocker zimelidine (20 mgkg‐1i. p.) and by the serotonin synthesis inhibitorp‐chlorophenyl‐alanine (300 + 300+ 150 mgkg‐1i. p. 72, 48 and 24 h before test). It is concluded that PCA given intrathecally releases serotonin from spinal terminals, which may under certain condit