The historically most important mechanistic theories attributed the fundamental cause of anesthesia to interactions betweeen anesthetics and proteins as early as the 1870s. According to the underlying thought, the resulting changes in the consistency of cellular protoplasm were the cause of the anesthetized state of the whole organism.These protoplasm coagulation theories, as they were collectively referred to, brought the contemporary enthusiasm for protoplasm, the rapid advances in colloid chemistry and the unified theory of narcosis proclamed by Claude Bernard under a unified mechanistic theory that reflected the Zeitgeist of the epoch.This research effort, on the intersection of the developing disciplines of cellular biology and colloid chemistry, lasted for almost a century. It involved scientists of worldwide reputation and resulted in a number of elegant theories. Contrary to widespread opinion, proteins and not lipids were recognized and investigated first as the critical molecular target of anesthetics more than a century prior to their much publicized rediscovery in 1984.The protoplasm coagulation theories of anesthesia were pursued after the First World War across ideological trenches by scientists in Europe, the Soviet Union and the United States. They united research in anesthesia with research of fundamental cell biology.In contrast to the much less fruitful lipid theories, protoplasm coagulation theories are largely forgotten without leaving a trace in contemporary discussions of the history of anesthesia. For many tyears, however, they constituted an essential part of fundamental anesthetic research and must therefore be mentioned in any historical review.