Potential exposure during mining and milling of uranium ore has resulted in the industry being highly regulated. Exposure can arise from inhalation of the daughter product radioactive gas radon (222Rn), inhalation of radioactive dust particles from mining and milling, direct irradiation from outside the body, and ingestion of radionuclides (e.g. uranium or radium) in food or water. Making use of the highly unusual lead isotopic signature for uranium ores (high 206Pb/204Pb from the high uranium content, low 208Pb/204Pb from the low Th/U ratio), we undertook a pilot study of nine male mine employees and three controls from the Ranger uranium mine in the Northern Territory Australia to determine if it was feasible to use lead isotopes in blood to identify exposure to uranium-derived materials. The lead isotopic data for the mine employees and controls plot in two distinct fields which are consistent with predicted isotopic patterns. Assuming retention of 10% of the ingested lead, then the increases seen in 206Pb represent intakes of between 0.9 and 15 mg, integrated over the years of exposure. The small amount of lead does not affect blood lead concentrations, but appears to be sufficient to be detectable with sensitive isotopic methods. Further studies, including those on urine, should be undertaken to confirm the veracity of the lead isotope method in monitoring exposure of uranium industry employees.