The administration of d-tubocurarine (dTc) to animals and humans has been reported to produce hypotension. Experiments in animals suggest that the hypotension is a result of both ganglionic blockade and histamine release. In order to determine the role of histamine release in dTc-induced hypotension in humans, the authors developed a sensitive radioenzymatic assay for plasma histamine and measured plasma histamine following dTc administration (0.25-0.75 mg/kg) to 21 surgical patients. While neither fentanyl (3 microgram/kg) nor thiopental (6 mg/kg) produced a significant change in plasma histamine, dTc caused a dose-dependent increase in plasma [dose dTc vs. log (plasma histamine), r = 0.62 P less than 0.003]. The log (plasma histamine) correlated with the dTc-induced hypotension (r= 0.61, P less than 0.005). The data suggest that histamine release is an important factor in the hypotension accompanying dTc administration in humans.