Using a new, highly sensitive and specific method for the determination of histamine in human plasma, it was shown that release of histamine followed injection of propanidid and thiopentone. Observations of gastric secretion, arterial pressure and pulse rate supported these findings. In normal persons the release of histamine had no special clinical significance. On the other hand, when anaphylactoid reactions occurred following propanidid injection histamine release was so massive as to explain the severe clinical signs and symptoms observed. In this study no reactions occurred following thiopentone injection. Although it seems likely that massive histamine release can occur during anaphylactoid reactions with this anaesthetic, we have no observations to confirm this. In one case it was shown that premedication with glucocorticoids and anti-histaminics and therapy with plasma substitutes could prevent the development of a severe reaction.