This investigation was designed to determine whether the narcotic alfentanil, a relatively new fentanyl derivative with rapid onset of action and offset of activity, alone or in combination with midazolam has advantages over the traditional meperidine and midazolam regimen for conscious sedation. Thirty-five subjects were randomized to receive an initial dose of narcotic and sedative with additional narcotics or sedatives administered as needed. Subjects receiving no midazolam sedative (alfentanil and placebo group, n = 13) had less desaturation and had the need for supplemental oxygen less often than those receiving alfentanil and midazolam (n = 11) or meperidine and midazolam (n = 11). There were no differences as assessed by patient and colonoscopist for tolerance and discomfort, procedure ease, recovery time, complications, electrocardiogram, and blood pressure. Baseline evaluation did not predict the need for supplemental oxygen. We concluded that alfentanil, with or without a sedative, has no advantage over the commonly used meperidine and midazolam regimen.