Objective: To determine if there is an association between occupational exposure to external ionizing radiation and leukemia mortality among civilian Portsmouth Naval Shipyard workers after potential confounders and effect modifiers such as solvent exposure, and time since exposure are considered. Methods: This study employs a nested case-control design and includes 115 leukemia cases and 460 controls. Among the cases and controls, 201 (35%) were monitored for radiation exposure. Badge doses and exposures to work-required medical x-rays were included in the analysis. Benzene and carbon tetrachloride exposure was assessed using workers' job information and industrial hygiene records. Conditional logistic regression was used to analyze the exposure-response relationship between external ionizing radiation exposure and leukemia mortality. Results: A significant positive association was found between leukemia mortality and external ionizing whole-body radiation exposure (OR= 1.08 at 10 mSv; 95% CI=1.01, 1.16) adjusting for gender, radiation worker status and solvent exposure duration. The latter factor (OR= 1.03 at one year of exposure; 95% CI=1.01, 1.06) was also significantly associated with leukemia mortality. The incorporation of estimated doses from work related medical x-ray exposures did not change the leukemia risk estimate. Significantly different exposure-response trends were observed in the 2.5 - 5 years since last exposure category compared to the> 10 years since last exposure category. The choice of categories for time since last (radiation) exposure (TSLE) classification did not greatly alter these findings. In this study the results using a linear ERR model estimate an excess relative risk of 23% (95% CI = 3%,88%) per 10 mSv of external radiation exposure from occupational sources after potential confounders were considered in the analysis. The excess relative risk has previously been estimated at between -4.1 % and 19.0% at 10 mSv in other epidemiologic studies of workers exposed to penetrating ionizing radiation (Fraser et al., 1993) and approximately 4% for individuals in the Japanese Life Span Study who were simultaneously exposed at various ages and developed diseases at different times after exposure (BEIR V,1990; Schubauer-Berigan and Wenzl, 2001). Conclusion: We observed a positive association between leukemia mortality and increasing external whole-body ionizing radiation exposure, adjusting for radiation worker status and solvent exposure duration. A significant exposure response between leukemia mortality and the duration of time workers were employed in job categories where solvent exposures were probable was also observed. However, solvent exposure was not a confounder of the association between radiation exposure and leukemia risk.