The ability of five antagonists to prevent the central nervous system's depressant effects of amitraz in dogs was evaluated using a shuttle avoidance paradigm. All drugs were injected iv into six male dogs trained to avoid a 1-mA shock by jumping over a hurdle within 10 sec of the start of a tone. Dogs were given an antagonist or saline followed in 5 min by 3 mg/kg amitraz dissolved in dimethyl sulfoxide (DMSO) or DMSO alone. After pretreatment with saline, amitraz decreased significantly the means number of avoidance responses and increased significantly the means latencies of avoidance responses. After pretreatment with the alpha 2-adrenoreceptor antagonist yohimbine (0.1 mg/kg), amitraz no longer decreased the means number of avoidance responses or lengthened the means latencies of avoidance responses. The nonselective alpha-adrenoreceptor antagonist tolazoline (3.3 mg/kg) prevented amitraz-induced increases in means latencies, but did not prevent the decreases in the means number of avoidances. The alpha 1-adrenoreceptor antagonist prazosin (1 mg/kg), the muscarinic receptor antagonist atropine (0.04 mg/kg), and the opioid receptor antagonist naloxone (1 mg/kg) did not prevent either of amitraz's effects. The data suggest that the amitraz-induced suppression of avoidance responding is mediated by alpha 2-adrenoreceptors rather than by alpha 1-adrenergic, muscarinic, or opioid receptors.