The cause of death after ingestion of a large dose of paraquat is unclear. We investigated the cardiovascular effects of paraquat injection in 7 dogs that were anesthetized with urethane and alpha-chloralose and maintained on controlled ventilation. After control measurements, paraquat (20 mg/kg) was injected iv. Average concentrations of plasma paraquat were 128 micrograms/ml at 15 min (point 1) and 44 micrograms/ml at 4 hr. The average time of survival was 5.5 +/- 2.2 hr. Comparison was made of control values, 15 min (point 1), and 2.5 +/- 1.0 hr before death (point 2). Pulmonary capillary wedge pressure (+33%) and pulmonary vascular resistance (PVR) (+28%) increased, but no change occurred in mean arterial pressure (MAP) or cardiac output (CO) at 15 min. Mean arterial pressure (-50%) and cardiac output (-61%) decreased, while total vascular resistance (+56%) and PVR (+256%) were increased at point 2. Arterial pH decreased from 7.394 and 7.307 (point 1) to 7.143 (point 2). The concentration of plasma catecholamines and lactic acid increased significantly at both points 1 and 2. Renal, adrenal and myocardial tissues were studied by light and electron microscopy. The outstanding feature was early swelling of mitochondria and disruption of the contents in the presence of intact mitochondrial membrane.