Using marine proteins and other antigens, Richet carefully documented the sudden drop in blood pressure and breathing problems that occurred in dogs on re-exposure. He argued that immunity can work not only as “prophylaxis” (protection) but also as its opposite, “anaphylaxis” (harm). This insight became the basis for understanding immediate-type hypersensitivity such as hay fever and food allergies. It also allowed physicians to foresee side effects during serum therapy and to introduce test doses and dilution strategies. Modern emergency measures like the EpiPen trace their conceptual roots back to Richet’s work.

In 1902 Richet, together with Paul Portier, sensitized dogs with sea-anemone toxin and observed that a second injection produced lethal shock within minutes. He coined the term anaphylaxis from the Greek ana (against) and phylaxis (protection), framing it as an over-activation of the immune response. He hypothesized that vasodilation, plasma leakage, and bronchospasm were mediated by histamine-like substances, paving the way for later research on chemical mediators. The idea linked to studies of serum sickness (Cochran), asthma (Priestley), and Cooke’s classification of immediate allergies, forming the backbone of modern allergology. Richet also stressed that understanding anaphylaxis was essential for managing risks in vaccine development and antitoxin serum therapy, thereby influencing public-health policy.

Richet employed diverse heterologous proteins—actinotoxin, equine serum albumin, snake antivenom—to quantify the rapid haemodynamic collapse appearing on re-exposure within 21 days of sensitization. Blood-pressure tracings and respiratory curves led him to attribute lethality to a simultaneous drop in peripheral vascular resistance and pulmonary vasoconstriction, rejecting the prevailing cardiac-depression hypothesis. He demonstrated that minute priming doses suffice and that the response scales exponentially with antigen quantity, suggesting a “negative sensitization” pathway distinct from classical immune memory. His findings paved the way for the Prausnitz–Küstner test, in which a soluble factor (later identified as IgE) was implicated. Richet also devised an in-vitro rat-intestinal contraction assay, proposing early on that mediator release underlies anaphylaxis. These experimental frameworks directly inspired the later development of histamine-receptor antagonists and mast-cell stabilizers.