The study investigated the effect of a slow-release formulation of zuclopenthixol acetate (Acunil®) on blue wildebeest (Connochaetes taurinus) in captivity. Two groups of trials were conducted using either Acunil or a placebo (control). Animals (Acunil: n = 17; placebo: n = 12) were observed for a 12-hr period before the administration of Acunil or the placebo (pretreatment). After 24 hr, animals were administered Acunil (1.5 mg/kg) or a placebo (1.0–3.0 ml of sterile water) and observed again for 12 hr (posttreatment). During both treatments, animals were stimulated every 2 hr for 1 min by a person entering the enclosure (referred to as periods of stimulation). Behavioral observations and continuous heart rate, respiration rate, and motion measurements were taken throughout. Animals treated with Acunil spent more time lying with their heads folded back, eating and standing with their heads down, and less time being vigilant and exploring while walking around. Animals treated with the placebo also spent less time being vigilant and more time lying with heads up. Animals treated with Acunil groomed less while standing and performed less head shaking; no such changes were observed in the control group. Neither Acunil nor the placebo had any effect (P > 0.05) on heart rate. However, overall mean respiration rate was lowered (P = 0.02) when animals were treated with Acunil (pretreatment: 14.5 ± 0.82 breaths/min; posttreatment: 12.5 ± 0.83 breaths/min). Acunil also caused a lowered (P < 0.05) respiration rate during periods when animals were stimulated (pretreatment: 16.2 ± 0.87 breaths/min; posttreatment: 13.7 ± 0.87 breaths/min) and when animals were trotting and being vigilant. No such changes were observed with the placebo. Both placebo- and Acunil-treated animals spent more time being stationary during periods of stimulation. However, Acunil-treated animals also spent less time moving fast when they were stimulated.