ABSTRACT: Hypoxia, which occurs frequently in aquatic ecosystems and is mainly due to increasing eutrophication can cause severe environmental stress in fish. We investigated experimentally the hypothesis that hypoxia could be one of the environmental stress factors that can induce papillomatosis in fish. Male roach Rutilus rutilus exposed to periodic oxygen deficiency and accompanied temperature increases (OT group) showed the highest increase in the intensity of papillomatosis, as measured by the number of scales covered by papillomatosis tumors. The second highest increase in disease intensity was among male roach exposed to periodical temperature increases. The incidence of such tumors was lowest in the control group, which was exposed to neither hypoxia nor increased temperature. The mortality of fish during the 17 d experiment was highest and the condition factor was lowest in the OT group, indicating this group experienced a higher level of stress. The apparent interaction of hypoxia and temperature suggests that these environmental stressors are among the multifactorial elements leading to papillomatosis in roach. Furthermore, these results provide experimental evidence to indicate that hypoxia may contribute to tumor development in fish.