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Although macromolecular fouling of microfiltration membranes is one of the critical factors governing the performance of these filtration processes, there is still little fundamental understanding of the underlying phenomena that influence the initiation, rate, and extent of fouling. We have obtained experimental data for the flux decline during the stirred cell filtration of different commercial preparations of bovine serum albumin (BSA) through asymmetric polyethersulfone microfiltration membranes. The fouling characteristics of these commercial solutions varied substantially, with the flux decline directly related to the technique utilized to initially precipitate and prepare the BSA. Prefiltration of BSA solutions prior to microfiltration substantially reduced their fouling tendency, with the degree of improvement increasing as the prefiltration was performed through smaller molecular weight cut-off membranes. The protein solutions were also characterized using gel permeation chromatography (GPC), with the fouling tendency of the different BSA preparations highly correlated with the concentration of BSA dimers and other high molecular weight species present in these BSA solutions. These results suggest that BSA fouling of these microfiltration membranes is associated with the deposition of trace quantities of aggregated and/or denatured BSA, with these fouling species serving as initiation sites for the continued deposition of bulk protein.