Inadvertent intra-arterial injection of drugs produces a well-defined clinical syndrome whose pathophysiology remains unclear. This study was designed to determine the role of the inflammatory mediator, thromboxane, in intra-arterial drug injections. The rabbit ear model, as described by Kinmonth and Sheppard, was used. Five of the experimental groups were treated with specific or nonspecific thromboxane blocking agents and two groups served as controls. Immunohistochemical staining of the control ears showed elevated levels of thromboxane within the first 6 hours postinjury. The specific thromboxane blocking agents, methimazole and Aloe vera, showed almost complete blockade of thromboxane production. The percentage of ear survival was significantly greater in the group treated with topical Aloe vera (p less than 0.05) and even greater survival was achieved in the combined Aloe vera/methimazole group (p less than 0.01). On the basis of these results, we have begun treatment of such injuries with specific and nonspecific thromboxane blocking agents.