Handling stress and capture myopathy are important consequences of intensively managing wildlife species. Over the last 15 yr, the use of long-acting neuroleptic (LAN) drugs in wildlife has increased, and these drugs have become a valuable tool for decreasing capture and handling stress in many species. At this time, reports on the use of these drugs in North American species are limited. The major objective of this study was to evaluate the use of the LAN, zuclopenthixol acetate (Clopixol-Acuphase), to decrease both quantifiable and subjective measurements of stress and activity in wild wapiti (Cervus elaphus, North American elk). This blinded, randomized study took place in February 1999 in Manitoba (Canada) and involved 11 animals receiving the drug and 12 animals acting as controls. At 24 hr after drug administration, there were measurable and significant decreases in the stress and activity of treated animals versus controls during handling.