Clearance rate (CR) response of Mytilus galloprovincialis was determined over 32 experiments in which the trophic conditions of its natural habitat, the Galician rías (Spain), were reproduced. Experimental diets were prepared by mixing pulverized sediment, Tahitian Isochrysis aff. galbana, and pulverized Spartina sp., avoiding multicollinearity among the seston variables used to characterize the diets: total particulate matter (TPM), quality (f = particulate organic matter (POM)/TPM), and chlorophyll content. This approach allowed us to identify the seston variables that have the most important effect on CR, as well as develop a mathematical model of CR response to the environmental trophic characteristics, without worrying about the statistical problems associated with multicollinearity among explanatory variables. Each of the three seston variables had a significant effect on CR response. Maximum CR was observed at a seston concentration of 1.2 mg L–1. The CR was inversely correlated with the fraction of low digestible organic matter (fdet = POMSpartina sp./TPM), and was relatively consistent when poorly digestible diets (fdet > 0.4) were excluded from the analyses. This relative stability suggested that CR was regulated by a physiological feedback such as the fraction of poorly digestible organic matter.