The effects of prolonged exposure to low-concentration combinations of halothane and nitrous oxide on tumor incidence, especially with regard to the reticuloendothelial system, were studied. Three groups of 50 male and 50 female Fischer 344 rats each were studied. For seven hours/day, five days/week, for 104 weeks, Group I was exposed to filtered air (control); Group II, to halothane, 1 ppm, and nitrous oxide (N2O), 50 ppm; Group III, to halothane, 10 ppm, and N2O, 500 ppm. No evidence of exposure-related effects on body weight, appearance, behavior, survival, or hematologic findings was found. Histologic evaluation of the reticuloendothelial system and of other major organs revealed neither enhancement of the spontaneous tumor rate nor any unusual neoplasm. Thus, this study did not lend support to the hypothesis that these anesthetic agents in low concentrations are responsible for the reportedly higher than average incidence of reticuloendothelial malignancies in operating room personnel.