The water soluble benzodiazepine derivative, midazolam, is used almost exclusively at our institution to produce sedation for numerous surgical procedures. Mild arterial oxygen desaturation has been reported in patients who have received as little as .04 mg/kg. A time series design study was undertaken to determine if there was any correlation between the decline in arterial oxygen percent saturation (SaO2) and the time at which sedation occurred and to establish the presence of any statistical significance in this decline. Thirty-one ASA I and II patients consisting of 8 females and 23 males requiring various minor orthopedic and general surgical procedures were studied. The total mean age of the population was 32.29 +/- 12.43 years (mean +/- SD). Fourteen patients had a smoking history, while 15 patients did not (2 patients were eliminated from the study for failure to demonstrate sedation, as characterized by either Verrill's sign or thickened speech following intravenous administration of midazolam). All patients arrived in the operating room unpremedicated and were administered .04 mg/kg midazolam intravenously. Arterial oxygen saturation was measured over a 10-minute period using pulse oximetry. Results were analyzed using regression analysis, a t-test for independent groups, and a one-way analysis of variance. There was no statistically significant difference in the decline in SaO2 between smokers and nonsmokers. Our study has shown that the mean onset of sedation using a dose of .04 mg/kg occurred between 3 and 4 minutes, with the peak fall in SaO2 occurring at the 3-minute interval irrespective of smoking history. The greatest mean drop in SaO2 was 95.84%. Midazolam, like its parent drug, diazepam, alters ventilatory mechanics.(ABSTRACT TRUNCATED AT 250 WORDS)