In a double-blind, randomized, placebo-controlled study of patients undergoing colonoscopy, sedation with an inhaled mixture of nitrous oxide/oxygen was compared with conventional intravenous sedation (pethidine 50 mg, midazolam 2.5 mg). In the patients studied, no significant differences were noted in number of pain episodes, need for additional intravenous sedation, or patient pain scores between the group receiving the nitrous oxide/oxygen mixture (n = 30) and those managed with conventional benzodiazepine/opiate injection (n = 29). Both methods were significantly more effective than placebo (n = 30). Six patients in the benzodiazepine/opiate group had oxygen desaturation, whereas none did in the nitrous oxide/oxygen group. Duration of stay after the procedure was significantly shorter in the gas inhalation group than in those receiving conventional intravenous sedation. Except for patients with severe chronic obstructive pulmonary disease, nitrous oxide/oxygen inhalation is a safe and acceptable alternative method of sedation and analgesia during colonoscopy.