Summary CFW mice, hyper sensitized to histamine by adrenalectomy, adrenal demed-ullation, treatment with histamine sensitizing factor (HSF) from Bordetella pertussis, or β-adrenergic blocking agents, are protected from histamine death by epinephrine or nor-epinephrine. Intravenous treatment with these drugs, to be maximally effective, should be given 30 to 60 seconds after histamine challenge. Mice made hypersensitive to histamine apparently die from an inability of their vascular system to overcome the hyportensive effects of histamine. In adrenalectomized or adrenal-demedullated mice, there is an insufficient production of catecholamines for protection, while in the HSF-treated or β-adre-nergically blocked mice the ability of endogenous catecholamines to protect seems to be diminished or blocked. When a sufficient quantity of exogenous epinephrine is given, the blocking effect of HSF or β-adrenergic blocking agents can be overcome and the mice protected from lethal histamine shock. When mice receive large sensitizing doses of HSF, protection with epinephrine is not possible.