Histamine and 5-HT have been demonstrated to be involved in pinnal anaphylaxis in mice. Each predominates at different stages during the 30-min development of the reaction. The main mediator of the early stage of the reaction (0-10 min) is histamine, that of the middle stage (10-20 min) is 5-HT, and that of the final 20- to 30-min stage is, again, histamine. The source and mechanism of release of the 5-HT and the late histamine are, as yet, unknown but under investigation.