Honey mesquite (Prosopis glandulosa) is distributed across a large portion of the southwestern United States. Ingestion of young leaves, pods, or beans can cause toxicosis in cattle and goats if they comprise a substantial portion of their diet. Goats, as browsers, are most likely to develolp mesquite toxicosis. Sheep appear to be more resistant to the plant's toxic effects. Consistent clinical signs include weight loss, ptyalism, mandibular tremors, tongue protrusion, and dysphagia. Diagnosis of mesquite toxicosis is largely made on the basis of history and clinical signs with exclusion of appropriate differentials. Laboratory findings are nonspecific but may reveal a mild anemia and hypoglycemia. Postmortem findings suggestive of mesquite toxicosis are limited to fine vacuolation of neurons in the trigeminal motor nucleus. Treatment consists of an alternative diet and supportive care. The disease is treatable in cattle and sheep but has a high case fatality rate in goats.