Arsine gas is a potent hemolytic agent. Concern about semiconductor workers prompted an in-depth study of arsine at the National Institute of Environmental Health Sciences to determine the hematopoietic effects of prolonged exposure to this gas. Female B6C3F1 mice were exposed by inhalation to 0, 0.5, 2.5, and 5 ppm arsine, 6 hr/day for 14 days. Body weights of exposed mice were comparable to those of controls, but a marked, concentration-related splenomegaly was observed. Higher level arsine exposure produced statistically significant decreases in red blood cells, hematocrit and hemoglobin, with increases in white blood cell counts and mean corpuscular volume of red blood cells. Erythropoiesis as measured by quantitation of erythroid precursors in culture revealed a marrow reduction of colony-forming unit erythroids/femur cells for all treated groups on Day 3 postexposure and only at the 5 ppm dose group on 24 days postexposure, while splenic erythropoiesis increased at higher concentrations of arsine. There was no alteration in bone marrow cellularity and a less significant effect on granulocyte-macrophage progenitors. A 12-week study of arsine at 0, 0.025, 0.5, and 2.5 ppm (6 hr/day) by inhalation showed similar effects on hematopoiesis in mice. In conclusion, arsine exposure at low concentrations produces a stress on the hematopoietic system characterized by hemolysis, which persists for a prolonged period following exposure.