An in vitro biological assay system was utilized to evaluate the effects of cyclopiazonic acid (CPA) mycotoxin on turkey cardiac papillary muscle performance. Acute exposure to 6 ug CPA/ml of bathing solution significantly decreased five performance criteria of in vitro papillary muscles. These criteria were; maximum weight a muscle could lift, maximum contraction velocity, maximum relaxation velocity, time to peak contraction and total time for muscle contraction and relaxation. These irreversible, altered performances appeared to be intracellular changes partially associated with calcium availability and suggested that physiopathological changes had occurred following acute CPA exposure. A second study demonstrated similar decreases in in vitro muscle performance which were compared with pathological changes. Electron photomicrographs demonstrated that the CPA exposed muscles evaluated in the biological assay system had increased numbers of swollen or lysed mitochondria. Irreversible decreased muscle performance and altered mitochondrial morphology were attributed to altered calcium and ATP availability. Two acute in vivo studies were designed to establish a dose response curve and assess the toxicological changes seen in turkey poults exposed to CPA. These are the first reports of CPA toxicity in turkey poults. Poults were given oral doses of 0, 5, 10, or 20 mg/kg/d for 2 days. Poults given 20 mg/kg/d were sacrificed in extremis 30 h after initial exposure. Clinical signs included: lethargy, ataxia, drooped head and wings, ruffled feathers, marked anorexia, and watery feces of reduced amounts. Total serum proteins and albumin were decreased by CPA ingestion. Major gross lesions noted at necropsy occurred in the gastrointestinal tract and liver. Poults receiving 10 and 20 mg/kg/d had focal erosions in the proventriculus and ventriculus, a fibrino-gelatinous membrane present in the ventriculus, and decreased liver weights. Hematological changes were leukocytosis, heterophilia, and lymphocytosis. Histopathologic changes included mucofibrinous necrotizing proventriculitis and ventriculitis, acute multifocal erosive enteritis and mild multifocal granulomatous hepatitis with bile duct proliferation. Body weight, feed consumption and water intake were significantly decreased by CPA ingestion. No cardiac ultrastructural changes were noted.