The effects of chronic exposure to dioxin (2,3,7,8,-tetrachlorodibenzo-pdioxin [TCDD]) and a dioxin-like compound (3,3',4,4',5-pentachlorobiphenyl [PCB126]) on the cardiovascular system were evaluated in female Harlan Sprague-Dawley rats as part of an ongoing National Toxicology Program investigation. The animals were gavage treated 5 d per week with up to 1000 ng of PCB126 per kilogram of body weight per day or up to 100 ng of TCDD per kilogram of body weight per day for up to 2 yr. The control animals received only a corn oil/acetone vehicle (99:1 mixture). The corresponding stop-study groups received the highest doses for 31 wk and then received only the vehicle for the remainder of the study. After a full necropsy of all animals, a complete set of tissues was examined microscopically. Administration of each compound was associated with treatment-related increases in the incidences of degenerative cardiovascular lesions. Cardiomyopathy and chronic active arteritis increased in a dose-related manner in all groups treated with PCB126 or with TCDD. Increased incidences were also observed in the stop-study groups, indicating that a shorter term exposure may produce some effects. The average severity of cardiomyopathy was minimal or slightly greater in all dose groups, including the controls. Chronic active arteritis occurred primarily in the mesentery and pancreas, although the rectum, liver, heart, ovary, uterus, and glandular stomach in the PCB126 study and the liver and ovary in the TCDD study were affected in a few of the dosed animals. The authors' investigations indicate that the rat cardiovascular system is a target for dioxin toxicity, which increases the incidence of spontaneous cardiomyopathy and arteritis.