The effect of administration of hydroxylamine (HA) to male and female mice was studied because of reports suggesting an anticarcinogenic effect and an enhancement of lifespan. In this study, two C3H sublines were used: the C3H/HeN which carries a germinal provirus of the mouse mammary tumor virus and the C3H/HeJ(+) which also carries the milk-transmitted exogenous virus. Lifetime administration of 10 mM HA in the drinking water resulted in a decrease in mammary neoplasm incidence in female C3H/HeN mice, but not in female C3H/HeJ(+) mice. Ovarian neoplasms and cysts were common in all groups, indicating ovarian dysfunction, but these were not affected by treatment. The incidences of other cryptogenic neoplasms found in controls in significant numbers, i.e. liver carcinomas, lymphomas, lung adenomas and adrenal cortex tumors were only marginally affected by the treatment. However, an increased incidence of vascular neoplasms of the spleen in hydroxylamine-treated female C3H/HeN mice and vascular neoplasms of the lymph nodes in hydroxylamine-treated male C3H/HeJ(+) mice indicated a subline-related action on the reticuloendothelial system. The survival of control mice was 35-58% at 2 years and this was not increased in either subline by hydroxylamine, which is interpreted to indicate that this antiioxidant does not increase lifespan of animals under conditions of maintenance that are adequate for good survival.