Risk assessment procedures use toxicity tests in which organisms are subjected to chemicals under otherwise constant and favorable experimental conditions. Because variable and suboptimal environmental conditions are common aspects of natural ecosystems, the hazard of underestimation of risk arises. Therefore, an uncertainty factor is used in the extrapolation of results of standard toxicity tests to field situations. The choice for these uncertainty factors is based on little ecological evidence. This review discusses studies on the toxicity of various chemicals to aquatic organisms, modified by temperature, nutritional state and salinity, excluding papers on changes in bioavailability of compounds. Collected data were analyzed quantitatively to evaluate the validity of toxicity data obtained from standard toxicity tests in the laboratory under field conditions. Generally, organisms living under conditions close to their environmental tolerance limits appeared to be more vulnerable to additional chemical stress. Usually, increasing temperature and decreasing food or nutrient level raised toxicity. The influence of salinity was less clear; metal toxicity increased with decreasing salinity, toxicity of organophosphate insecticides increased with higher salinity, while for other chemicals no clear relationship between toxicity and salinity was observed. The interactions can be explained by several physical and physiological processes, acting on factors such as bioavailability, toxicokinetics, and sensitivity of organisms. Quantitative analysis of data indicated that an uncertainty factor for the laboratory to field extrapolation should be smaller than one for an ecosystem in a temperate region, while a factor greater than one would be appropriate for systems nearby discharge points of cooling water. The factor should be greater than one when varying nutritional state is concerned, but smaller than one with respect to salinity. Dependent on the effect parameter used, the differences in toxicity between laboratory and relevant field situations ranged from a factor of 2.6 to 130 and 1.7 to 15 for the two temperature conditions and 1.2 to 10 for nutritional state. A salinity increase from freshwater to marine water decreased toxicity by a factor of 2.1. However, as less extreme salinity changes are more relevant under field conditions, the change in toxicity is probably much smaller. To obtain uncertainty factors that sufficiently protect natural systems without being overprotective, additional research is required.