The goal of this project is to identify and evaluate factors that may influence tumor incidence in laboratory rodents. We continued to investigate the impact of body weight differences on tumor incidence. We found that food restricting dosed and control animals to achieve idealized body weights in both groups may produce false positive outcomes if substantially more food restriction is required for control groups than for dosed animals. We also found that equal food restriction to dosed and control animals may produce false negative outcomes if the resulting body weights are substantially different in dosed and control groups. We also investigated the association between the severity of chronic progressive nephropathy (CPN) and the incidence of adrenal pheochromocytoma in male F344 rats. In control animals the incidence of pheochromocytoma was consistently higher in those animals with the more severe CPN. However, this correlation was not consistently observed in dosed groups. For example, among 28 NTP studies reporting a chemically-related increased severity of CPN, only three had a significant increase in pheochromocytoma. On the other hand, 5/6 NTP studies with increased incidence of pheochromocytoma had some degree of increased CPN severity. We concluded that this association may be a factor in the interpretation of some NTP studies. - Variability; tumor incidence; rodent carcinogenicity bioassays; body weight; dietary restriction. nephropathy, adrenal pheochromocytoma