A mechanistic model was derived for direct flow microfiltration (MF), one which lends more insight into the factors that control MF performance compared to a statistical curve-fitting procedure that is often used to estimate chemical cleaning intervals at pilot-scale. This theoretical approach to MF fouling was based on fundamental feed water, membrane, and cake characteristics and was shown to predict well pilot-scale experimental specific flux profiles when backwash effectiveness is used as a fitting parameter. Long-term experimental specific flux profiles obtained during the constant flux filtration of natural colloidal materials are reported under conditions typical of water treatment applications. Cakes formed during the filtration of untreated surface waters were found to be highly resistant and compressible. Longer chemical cleaning intervals (and higher values of the backwash ef fectiveness parameter) were obtained during the constant flux filtration of natural colloidal materials by a decrease in flux, feed water turbidity, and/or backwash interval.