Several experimental and clinical studies have suggested that histamine is released following the administration of neuromuscular blocking agents, and that the histamine release is an important aspect in the hemodynamic response to the drug. We have measured plasma histamine following the administration of a series of neuromuscular blocking agents in man. Our data suggests that members of this class of drugs can cause a dose dependent release histamine release in man and that this release is hemodynamically significant. We have also evaluated the roles of rate of administration, of pretreatment with H1 and H2 antagonists and alterations in drug design as clinical strategies in attenuating the adverse reactions. The data obtained in humans can be shown to validate the cat model as a means of screening novel neuromuscular blocking agents.