Severe chronic itch and intractable pruritus are encountered frequently by dermatologists. Recent data suggest that generalized pruritus may result from an imbalance between the mu and kappa opioid systems, and kappa-agonists have been shown to inhibit pruritus in both animals and human beings. These findings led us to use butorphanol, a commercially available kappa-opioid agonist and mu-opioid antagonist. We present a case series of 5 patients with intractable pruritus associated with inflammatory skin diseases or systemic diseases who demonstrated rapid and marked improvement when treated with intranasal butorphanol. Because of the small, open-label nature of this study, butorphanol should be investigated further in a larger, randomized controlled trial.