OBJECTIVE To evaluate the effects of intravenous (IV) or intramuscular (IM) hyoscine premedication on physiologic variables following IV administration of medetomidine in horses. METHODS Randomized, crossover experimental study. METHODS Eight healthy crossbred horses weighing 330 ± 39 kg and aged 7 ± 4 years. METHODS Baseline measurements of heart rate (HR), cardiac index (CI), respiratory rate, systemic vascular resistance (SVR), percentage of patients with second degree atrioventricular (2(o) AV) block, mean arterial pressure (MAP), pH, and arterial partial pressures of carbon dioxide (PaCO2 ) and oxygen (PaO2 ) were obtained 5 minutes before administration of IV hyoscine (0.14 mg kg(-1) ; group HIV), IM hyoscine (0.3 mg kg(-1) ; group HIM), or an equal volume of physiologic saline IV (group C). Five minutes later, medetomidine (7.5 μg kg(-1) ) was administered IV and measurements were recorded at various time points for 130 minutes. RESULTS Medetomidine induced bradycardia, 2(o) AV blocks and increased SVR immediately after administration, without significant changes in CI or MAP in C. Hyoscine administration induced tachycardia and hypertension, and decreased the percentage of 2(o) AV blocks induced by medetomidine. Peak HR and MAP were higher in HIV than HIM at 88 ± 18 beats minute(-1) and 241 ± 37 mmHg versus 65 ± 16 beats minute(-1) and 192 ± 38 mmHg, respectively. CI was increased significantly in HIV (p ≤ 0.05). Respiratory rate decreased significantly in all groups during the recording period. pH, PaCO2 and PaO2 were not significantly changed by administration of medetomidine with or without hyoscine. CONCLUSIONS Hyoscine administered IV or IM before medetomidine in horses resulted in tachycardia and hypertension under the conditions of this study. The significance of these changes, and responses to other dose rates, requires further investigation.