The purpose of this study was to determine the influence of timing and concomitant administration of atropine and/or meperidine on the perioperative effects of oral midazolam in children. In 154 healthy children, 1-8 yr old, we studied six oral preanesthetic medication regimens according to a randomized, double-blind protocol. Group A (placebo) received 5 mL of apple juice. The other five groups received medication with apple juice to a total volume of 5 mL, 20-60 min before induction of anesthesia. Group B received atropine (0.02 mg/kg); group C received midazolam (0.5 mg/kg); group D received midazolam (0.5 mg/kg) and atropine (0.02 mg/kg); group E received meperidine (1.5 mg/kg) and atropine (0.02 mg/kg); and group F received meperidine (1.5 mg/kg), atropine (0.02 mg/kg), and midazolam (0.5 mg/kg). The sedative effect of midazolam was maximal 30 min after oral administration. Ninety-five percent of the children who were separated from their parents within 45 min after oral midazolam administration (with or without atropine) had satisfactory separation scores (vs 66% of those separated after 45 min; P less than 0.02). Midazolam-treated patients were more cooperative with a mask induction of anesthesia compared with non-midazolam-treated children (83% vs 56%). Neither atropine nor meperidine appeared to significantly improve the effectiveness of oral midazolam. No preoperative changes in heart rate, respiratory rate, or hemoglobin oxygen saturation were noted in any of the treatment groups. Finally, oral midazolam did not prolong recovery even after outpatient procedures lasting less than 30 min. In conclusion, midazolam (0.5 mg/kg) given orally 30-45 min before induction of anesthesia is safe and effective without delaying recovery after ambulatory surgery.