The effects of chronic exposure to JP-4 gas were evaluated in mice, rats, and dogs. Beagle dogs, F344-rats, and C57BL/6-mice were exposed to 500 and 1,000mg/m3 JP-4 for 90 days for 23 hours per day, which simulated worst case conditions for people. The dogs and one third of rodents were euthanized following exposure, and remaining rodents were held for 19 or 21 months to determine tumorigenesis. No clinical signs of toxic stress or mortality occurred during the 90 day exposure period. Gross examination of dogs found roundworm infections and mild inflammatory changes in lungs that were not JP-4 related. Histopathology of rats found hyaline droplet formation in kidneys of 100% of rats exposed to 1,000mg/m3 JP-4 and 96% of rats exposed to 500mg/m3 JP-4 compared with only 7% of control rats. In mice, hepatocellular fatty changes occurred in 89% of the low JP-4 group, 90% of the high JP-4 group, and 4% of controls. Kidney ultrastructure of JP-4 male rats showed hyaline, crystalloid intracytoplasmic inclusions in the proximal tubules, and the severity was greater in the high dose group. At 19 and 21 months, rats showed no hyaline droplets were seen, but instead, an increased incidence of medullary mineralization and hyperplasia of pelvic urothelium. Mice showed no changes at 19 and 21 months that differed from controls. The authors conclude that the most significant finding is increased renal disease in male rats.