SUBSTANCE P (SP)1 has long been known to have marked effects on the central nervous system (CNS). Lembeck2 suggested that SP might be a transmitter of primary sensory impulses, an hypothesis supported by subsequent investigators3,4. Early work on SP was carried out using natural material, which unless highly purified, is known to be contaminated with bradykin or some other kinin-like material5. As bradykinin also has marked effects on the CNS, experiments carried out using impure SP may be misleading. This may account for some of the conflicting observations that exist regarding the action of SP on sensory transmission, and may also explain its interaction with opioids. Whereas impure SP has been shown to antagonise morphine6, synthetic SP was found to substitute effectively for morphine in mice chronically treated with morphine7. SP does not act like morphine in the field-stimulated guinea pig ileum8 and does not combine with morphine receptors9. Furthermore, SP has been reported to be the most potent algogenic substance known on the human blister base10. Recent reports on the characterisation and activity of enkephalin11,12 suggested that enkephalin may be acting as an analogue of SP. We have therefore examined SP for morphine-like activity.