In both male and female Fischer rats, feeding 4-chloro-o-phenylenediamine at 0.5 or 1% in the diet led to a significant increase in hyperplasia, papilloma and carcinoma of the urinary bladder. Neoplastic nodules of the liver and squamous cell papillomas of the stomach were also increased slight. Similar levels of this compound in male and female B6C3F1 mice increased significantly the incidence of hepatocellular adenomas and carcinomas. 4-Chloro-m-phenylenediamine at 0.2 or 0.4% in the diet led to a significant elevation in the incidence of adrenal pheochromocytoma in male rats. At 1 or 2% levels it caused hepatocellular adenoma in female mice. Although the analog, 2-chloro-p-phenylenediamine increased transitional cell hyperplasia of the kidney in both male and female rats, it had no significant neoplastic effect at the 0.15 or 0.3% levels fed.