The hypertrophic conditions of several confined areas in the Lagoon of Venice are but one of the consequences of nutrient discharges from its drainage basin. The monthly distribution of these loads, as well as their spacial subdivision among different tributaries of this characteristic water body, directly affect the growth cycle of macroalgae in it. The magnitude of these loads cannot be precisely measured by direct methods, however, it can be estimated by simulation with appropriate models. A comprehensive study aimed at the determination of these loads is under way as part of a larger intervention program to restore the physical and ecological equilibrium of the Lagoon. This paper focuses on the results of the simulation of diffuse loads generated in the Lagoon watershed. These results were obtained by interfacing a geographical information system (GIS) of the watershed and two models simulating respectively urban and agricultural diffuse pollution. Diffuse loads are then compared with the corresponding point sources to evaluate their relative contributing role in the dystrophic behavior of the Lagoon. The relative importance of diffuse sources is discussed with particular reference to time and space variability of the loads.