The relative influence of substance properties and of environmental characteristics on the variation in the environmental fate of chemicals was studied systematically and comprehensively. This was done by modeling environmental concentrations for 200 sets of substance properties, representative of organic chemicals used, and 137 sets of environmental characteristics, representative of regions in Europe of 250 × 250 km. Since it was expected that the model scale has an influence on the predicted concentration variations, the calculations were repeated for regions with a 100 × 100 km and 50 × 50 km area. Stepwise multiple regression analysis was performed to determine the contribution of each of the individual input parameters on the total concentration variation. Depending on the scenario, the range in predicted environmental concentrations spreads from two up to nine orders of magnitude. In accord with earlier studies, variation in the fate of chemicals in the environment appeared to depend mainly on substance-specific partition coefficients and degradation rates. For the estimation of soil and water concentrations with direct emissions to these compartments, however, the influence of spatial variation in environmental characteristics can mount up to two orders of magnitude, a range that can be significant to account for in certain model applications. Concentration differences in water and soil are predicted to be larger if a smaller region is applied in the model calculations, and the relative influence of environmental characteristics on the total variation increases on a more detailed spatial scale. It is argued that the influence of environmental characteristics as predictors of exposure concentrations of chemicals deserves better attention in comparative risk assessment with conventional nonspatial multimedia box models.