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Purpose: This prospective, double-blind, placebo-controlled study was designed to determine the efficacy of nitrous oxide (N(2)O) in alleviating the pain that followed sequential injection of propofol and rocuronium., Methods: A total of 205 adult patients (age, 18-68 years) received one of the following combinations: NaCl and 100 % O(2) (group C); 0.5 mg/kg lidocaine and 100 % O(2) (group L); NaCl and a mixture of 67 % N(2)O/O(2) (group N); or 0.5 mg/kg lidocaine and a mixture of 67 % N(2)O/O(2) (group LN). Vein occlusion was released after 1 min, and 5 ml propofol was injected over 10 s. Pain was evaluated on a visually enlarged, laminated, numeric rating (0-10) scale. The remainder of the induction dose of propofol (with a 3-ml bolus of normal saline and 0.6 mg/kg rocuronium) was then injected. The response to the rocuronium injection was assessed with a four-point scale (0-3)., Results: The incidence and severity of pain from the propofol injection in groups L, N, and LN were significantly lower than those in group C (P < 0.001). Frequency and intensity of the withdrawal response were significantly less in groups N and LN than in groups C and L (no response, P < 0.001; severe response, P < 0.001)., Conclusions: Pretreatment with inhaled N(2)O can reduce the pain associated with propofol and rocuronium injection. Moreover, N(2)O (with or without lidocaine) is more effective than lidocaine alone in reducing rocuronium-related withdrawal reactions associated with sequential injection of propofol and rocuronium.