In order to assess the potential chronic toxicity and tumorigenicity of ammonium perfluorooctanoate (APFO), a 2-year dietary study was conducted with male and female rats fed 30 ppm or 300 ppm (approximately 1.5 and 15 mg/kg). In males fed 300 ppm, mean body weights were lower across most of the test period and survival in these rats was greater than that seen either in the 30 ppm or the control group. Non-neoplastic effects were observed in liver in rats fed 300 ppm and included elevated liver weight, an increase in the incidence of diffuse hepatocellular hypertrophy, portal mononuclear cell infiltration, and mild hepatocellular vacuolation without an increase in hepatocellular necrosis. Mean serum activities of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were elevated up to three times the control means, primarily at the 300 ppm dose. A significant increase in Leydig cell tumors of the testes was seen in the males fed 300 ppm, and tumors of the liver and acinar pancreas, which are often observed in rats from chronic exposure to peroxisome proliferating agents, were not observed in this study. All other tumor types were those seen spontaneously in rats of this stock and age and were not associated with feeding of APFO.