To assess the potential of the epiphyton community for monitoring spatial and temporal variations in the environmental quality of freshwater ecosystems, this paper describes the response of epiphytons to ecological and toxicological factors in Lake Saint-François, a fluvial lake of the St. Lawrence River (Québec). First, community descriptions and biotic indices based on size structure and on taxonomic composition were compared to test if size could usefully describe epiphyton response to environmental factors. Secondly, the relative contribution of ecological and toxicological variables in explaining the variation observed in epiphyton was quantified. A size-based approach classified the sites similarly to taxonomic analysis, but a larger portion of variance in size could be explained indicating a stronger relationship with environmental factors. Among both taxonomy and size-based biotic indices, the slope of the normalized size spectra performed best in terms of total explained variance. There were strong interactions between toxicological and ecological variables. These interactions should be considered in the planning and interpretation of biomonitoring studies. In such surveys, samples should be collected at sites with similar ecological characteristics: for example, the same macrophyte type and sediment texture. Interpretation of the data should consider the possible covariance of toxicological and ecological variables.