The effects of bolus administration of large doses of vecuronium on the onset and duration of neuromuscular blockade and histamine release were studied during fentanyl-nitrous oxide anesthesia. Forty adults were randomly assigned to receive a bolus injection of either 0.1, 0.2, 0.3, or 0.4 mg/kg of vecuronium. The evoked electromyogram of thumb adduction to train-of-four stimulation was monitored. The time of onset and clinical duration (mean +/- SEM) after each dose were as follows: 0.1 mg/kg, 164 +/- 27 s and 42 +/- 5 min; 0.2 mg/kg, 120 +/- 17 s and 68 +/- 8 min; 0.3 mg/kg, 88 +/- 17 s and 111 +/- 19 min; 0.4 mg/kg, 78 +/- 19 s and 115 +/- 19 min. Both time of onset and duration after doses of 0.3 or 0.4 mg/kg were significantly different from values after the lower doses. No dose-related changes in blood pressure, heart rate, or histamine release were observed. The authors conclude that large bolus doses of vecuronium can be safely used to speed the onset of blockade, but with a significantly prolonged duration of action.