Abstract Groups of male Sprague-Dawley rats received po doses of cyclopiazonic acid (CPA) on four consecutive days at 0.0, 0.2, 2.0, 4.0, or 8.0 mg kg −1 days −1. Clinical signs of toxicity were observed only in the two highest dose groups. Rats in the highest dose group exhibited abnormal behavior, diarrhea, and other signs of toxicity after several days of dosing, and most were moribund before the last scheduled dose was administered. Liver and spleen were more severely affected than other organs in the two highest dose groups. Livers contained diffuse pycnotic nuclei and, in some high-dose rats, focal areas of coagulative necrosis. In the highdose group aspartate and alanine aminotransferase activities were elevated, cytochrome P-450 concentration was decreased, and glutathione S-transferase activity was unchanged. Spleens were hemorrhagic and white pulp contained necrotic lymphocytes. White cell counts were decreased in a dose-related manner in the two highest dose groups. The gastrointestinal tract of high-dose rats contained pycnotic nuclei, and sites of necrosis were observed in stomach, but these lesions were limited to several animals, and were generally mild. Pathologic changes in conjunction with decreased feed and water intake probably contributed to the general deterioration of high-dose rats that resulted in death.