Nitrate from drinking water is converted in the body to nitrite by bacteria in the gut. This project examined effects of nitrate/nitrite on immune functions, i.e., human lymphocyte proliferation and cytokine production. Nitrate had no effect on lymphocyte growth, but nitrite decreased proliferation. Neither inhibited fibroblast growth. In 1/3 to 2/3 of the subjects tested, sodium nitrate or nitrite decreased production of Th1 cytokines (interleukin-2, interferon-gamma, and tumor necrosis factor-beta). Nitrate and nitrite either increased or had no effect on the production of the Th2 cytokine interleukin-10. A Th1 immune response is associated with resistance to a variety of infectious diseases; a Th2 response is associated with disease susceptibility. Because nitrate/nitrite shifted the balance from a Th1 to a Th2 response in some individuals, exposure to these compounds may decrease these persons' responsiveness to infectious diseases. The levels of nitrate used in this study are relevant to human health because they are present in the liquid portion (nonbreastfed) of some 2-month-old infants' diets in rural Romania.