The present study reanalyzed 46 existing uranium (U) chronic toxicity datasets for four freshwater species to generate consistent toxicity measures and explore relationships between U toxicity and key physicochemical variables. Dissolved organic carbon (DOC) was consistently the best predictor of U toxicity based on 10% inhibitory concentration (IC10) and median inhibitory concentration (IC50) values, with water hardness also being a significant co-predictor of IC50 concentrations for one species. The influence of DOC on acute and chronic U toxicity was further characterized using existing data for five species, and was found to vary depending on species, DOC source, and exposure duration (acute vs chronic). The slopes of the relationships between DOC and (normalized) acute and chronic U toxicity were modeled using cumulative probability distributions. From these, slopes were selected for which to correct acute or chronic U toxicity values or hazard estimates based on the aquatic DOC concentration. The fifth percentiles of these cumulative probability distributions for acute and chronic exposure data were 0.064 and 0.090, respectively, corresponding to a 6.4 and 9.0% reduction in U toxicity relative to the toxicity at the base DOC concentration for each 1 mg/L increase in DOC concentration (over the DOC range 0-30 mg/L). Algorithms were developed to enable the adjustment of U toxicity values and U hazard estimates, depending on DOC concentrations. These algorithms will significantly enhance the environmental relevance of water quality/risk assessments for U in fresh surface waters. Environ. Toxicol. Chem. 2012; 31: 2606-2614. © 2012 SETAC.