Experiments were performed to assess the responsiveness of vessels subserving bone tissue to nerve stimulation and to exogenously administered catecholamines and acetylcholine. Tibias of mongrel dogs were isolated and dissected free; the periosteum was left intact. The main nutrient artery was prepared and cannulated. Ring electrodes were placed around the artery. The preparation was perfused at constant flow with aerated (95% O2 - 5% CO2) Krebs-Ringer solution (37 degrees C) by means of a roller pump. The perfusion pressure was continuously recorded. For each preparation, the flow rate was used at which the response to a standard dose of norepinephrine was the largest. Periarterial electrical stimulation caused frequency-dependent increases in perfusion pressure; because these responses were blocked by phentolamine, they must be due to activation of sympathetic nerves. Injections of norepinephrine caused dose-dependent increases in perfusion pressure that were abolished by phentolamine. Acetylcholine caused dose-dependent, atropine-sensitive decrease of the constrictions caused by norepinephrine infusions. These experiments demonstrate that the isolated perfused tibia of the dog is a satisfactory preparation to investigate the direct effects of sympathetic nerve stimulation and naturally occurring vasoactive amines on bone blood vessels.