The administration of d-tubocurarine (dTC) to animals and humans was reported to produce hypotension. Experiments in animals suggest that the hypotension is due to ganglionic blockade and histamine release. To determine the role of histamine release in dTc-induced hypotension in humans, a sensitive radioenzymatic assay for plasma histamine was developed and plasma histamine after dTC administration (0.25-0.75 mg/kg) was measured in 21 surgical patients. Fentanyl (3 .mu.g/kg) and thiopental (6 mg/kg) did not produce a significant change in plasma histamine, dTc caused a dose-dependent increase in plasma [dose dTc vs. log (plasma histamine), r = 0.62, P < 0.003]. The log (plasma histamine) correlated with the dTc-induced hypotension (r = 0.61, P < 0.005). Histamine release is an important factor in the hypotension accompanying dTc administration in human.