Non-steroidal anti-inflammatory drugs (NSAID) only partially inhibit the hyperalgesia in the inflammation induced by carrageenin in the hind rat paw, one of the most frequently used nociceptive tests. We now report that either the guanethidine depletion of peripheral sympathomimetic amines or the treatment with adrenoceptor antagonists (beta-blockers) and a specific dopamine (DA)-1 antagonist (SCH 23390) significantly reduced carrageenin hyperalgesia. These antagonists also abolished the rat paw hyperalgesia induced by several sympathomimetic amines as well as that induced by a selective DA-1 agonist, SKF 38393. Blockade of uptake-1 by cocaine potentiated the hyperalgesia induced by carrageenin and sympathomimetic amines. We conclude that there is a sympathetic component, possibly mediated by a DA-1 type receptor in carrageenin-induced hyperalgesia. This component may predominate in certain types of pain not sensitive to NSAID. If so, selective peripheral DA-1 antagonists could be developed as a novel class of analgesics.