Pretreatment of mussel processing effluents for citric acid production by Aspergillus niger (CBS 262-65) in submerged culture was studied by means of an orthogonal full factorial experimental design with four independent variables : initial levels of hexacyanoferrate II, methanol, phosphate, and carbon source. The empirical model thus obtained showed the ineffectiveness of the hexacyanoferrate treatment (contrarily that occurs with molasses) and at the same time, a series of complex interactions affecting the acid production not described in previous studies concerned by the separate effects of the variables here considered. Basically, the main effect of the hexacyanoferrate is toxic while the presence of methanol seems to involve morphological changes that increase the superficial area of the mycelial pellets, thereby promoting an unspecific metabolic activation. It therefore enhances the toxic effect of hexacyanoferrate, but also favors citric acid accumulation. The net response depends on the concentrations of the carbon sources and phosphorus.