Uranium (U) is a nonessential and toxic heavy metal and radionuclide. Nitric oxide (NO) and hydrogen peroxide (H2O2) are intimately involved in the growth, development and metabolic function of plant cells. In addition to possible toxic activities, a role for these signalling molecules in the regulation of plant responses to toxic metals has been proposed. Here, we investigated the synthesis of NO and H2O2 in Arabidopsis thaliana seedlings exposed to 25 µM U. We demonstrated that U induces NO and H2O2 production in the roots and leaves. Addition of the NO releasing compound, sodium nitroprusside (SNP) as well as the NO synthase inhibitor (L-NAME) to the plants, resulted in a decrease of the U-induced NO production and both alleviated U toxicity as indicated by plant growth (leaf area and biomass). Treatment with L-NAME further resulted in the disappearance of the U-induced H2O2 in the shoots of the plants. It appears that generation of NO and H2O2 is intimately linked in the toxicity response of U-exposed A. thaliana plants.