The algesic effect of substance-P with and without the addition of bradykinin or 5-hydroxytryptamine was studied in 13 healthy volunteers. Test substances dissolved in saline were injected into the temporal muscle and the forearm skin and the effects compared with those of saline. In the temporal muscle, none of the test substances induced more pain than saline, but substance-P with bradykinin lowered the pressure pain threshold by 18% (p less than 0.02). All test substances induced pain wheal and flare in the forearm skin. Substance-P induced a more pronounced flare reaction than bradykinin, whereas the latter induced more pain than substance-P. This dissociation between pain and flare may indicate that C-fibres in the human skin represent more than one type of nociceptor.