The role of the Nobel Laureate Henry Dale in the history of allergy and the association of anaphylactic conditions with the liberation of histamine is often overlooked. This paper examines his work in this field in the broader context of his researches into endogenous mediators of normal physiological and abnormal pathological functioning. It also assesses the impact of his working environment, especially the unique conditions he enjoyed at the beginning of the twentieth century in the Wellcome Physiological Research Laboratories . (...) The WPRL belonged to the pharmaceutical manufacturer Henry Wellcome, and it was the juxtaposition of the routine commercial obligation of testing drugs for Burroughs, Wellcome & Co., with the opportunities of pursuing unfettered physiological research in well-equipped and supported laboratories, that resulted in what Dale referred to as ‘happy accidents’ when one set of results suggested experimental strategies and designs to another circumstance. In this way an observation of an unusual effect of an extract of ergot of rye led to collaborative chemical and physiological explorations which revealed the presence of histamine, previously known only as a synthetic product. Further work, accidentally facilitated by the fact that the WPRL produced serum anti-toxins commercially and surplus horse serum was used in experiments where other physiologists routinely used saline, hinted that histamine played a role in the symptom complex known as anaphylaxis. This paper explores some of these themes and elaborates their significance. (shrink)