Summary Background Trema micrantha is a tree widely distributed throughout the Americas. The tree produces highly palatable leaves that have been associated with natural poisoning in goats, sheep and horses, in which hepatic necrosis and hepatic encephalopathy have been observed. Objectives This study describes malacia and haemorrhage in the central nervous system (CNS) due to T. micrantha consumption, with minimal to absent hepatic lesions. Study design Retrospective case series. Methods A total of 14 horses with a history of neurological signs and spontaneous consumption of T. micrantha leaves were submitted to necropsy and multiple samples were collected for histopathology. Details of clinical history and signs of the horses were obtained through inquiries to the owners and attending veterinarians. Results All the 14 horses had neurological signs of ataxia, severe sialorrhoea, involuntary running movements, sternal and lateral recumbency, and death after a clinical course that lasted from 24 h to 9 days. For a few days prior to onset of clinical signs, all horses had spontaneously consumed, potentially toxic doses of T. micrantha leaves. All 14 brains had diffuse yellowish discoloration affecting the rhombencephalon, mesencephalon, diencephalon, telencephalon and corpus striatum. In all cases, the most severe lesions were observed in the pons. Spinal cord lesions were observed affecting the lumbar intumescence, which was swollen with darken and depressed areas at the dorsal and ventral horns, and at the sacral level, which on cut surface displayed a friable and yellowish grey matter. The lesions observed grossly in brain and spinal cord consisted microscopically of severe vasculitis and liquefactive necrosis of white and grey matter of the brainstem, cerebellum and spinal cord. Main limitations This is a small retrospective series relying on clinical observations reported by owners and attending veterinarians. The mechanism of action of the plant toxin in the CNS is still unidentified. Conclusion T. micrantha poisoning in horses causes predominantly a neurological disease, with minimal to absent hepatic lesions.