The effects of butorphanol administered by a nasal spray (transnasal, TN) and by intramuscular (IM) injection were compared to determine the onset of action, relative potency, profile of effects, and relative abuse liability of TN butorphanol. TN/IM placebo and TN and IM butorphanol (1, 2, and 4 mg) were tested in seven male opioid abusers not currently physically dependent on opioids using a double-blind, double-dummy, Latin square design. Measures of subjective, behavioral and physiological response were assessed. The onset and duration of action of butorphanol administered by the IM and TN routes were similar at low doses, but onset of TN butorphanol 4 mg was slower than that of 4 mg IM. IM butorphanol produced miosis, some opiate-like behavioral and subjective effects, and increasing dysphoric sedation and perceptual effects with increasing dose. TN and IM butorphanol 1 and 2 mg produced effects that were qualitatively and quantitatively similar; however, TN butorphanol 4 mg was less potent than 4 mg IM. Pharmacodynamic evidence suggests that the abuse potential of TN butorphanol is not different from that of IM butorphanol.