A prospective, randomized, double-blind study was performed in 40 patients (ASA class I-III) treated with atracurium to ascertain whether histamine release caused hemodynamic or cutaneous changes. The treated group of 20 patients was premedicated with the H1 antagonist dimetindene (0.2 mg/kg) and the H2 antagonist ranitidine (1.25 mg/kg); the control group of 20 patients received saline. Six minutes after the induction of anesthesia with thiopental/fentanyl, patients received atracurium 0.5 mg/kg over 5 s. Plasma histamine levels were measured fluorometrically 5 min after administration of thiopental/fentanyl and 2 and 5 min after atracurium. Arterial blood pressure and heart rate were recorded every 2 min. Histamine levels (0.24 ng/mL) did not change significantly after thiopental/fentanyl. In the control group, 2 min after injection of atracurium, plasma histamine levels were 0.76 +/- 0.76 ng/mL, and in the antihistamine-treated group, 0.39 +/- 0.24 ng/mL (P < 0.05 control versus treated), suggesting that pretreatment with antihistamines may attenuate atracurium-induced histamine release. Systolic and diastolic blood pressure decreased significantly in both groups after thiopental (P < 0.05), but did not decrease further after the administration of atracurium. There were cutaneous manifestations in 7 of 20 patients in the control group and in none of the 20 patients treated with H1 and H2 antagonists (P < 0.0005). We conclude that atracurium caused modest histamine release in our patients but that the decrease in arterial blood pressure may have been due, in part, to thiopental. Cutaneous manifestations of histamine release did not correlate with hemodynamic events or with plasma histamine levels, but were prevented with antihistamine pretreatment.