The breakthrough of a model virus, bacteriophage PhiX-174, through normal-flow virus filters was studied using both commercial process fluids and model feed streams. The results indicate that (i) PhiX-174 is a reasonable model for a mammalian parvovirus [MMV (murine minute virus)] in virus filtration studies; (ii) PhiX-174 LRV [log(reduction value)] shows a better correlation with percentage flow decline compared with volume processed under a variety of conditions; (iii) although the extent of decline in virus LRV is dependent on the mechanism of filter fouling, the fouling mechanisms operative in a viral validation study are representative of those likely to be found under actual production conditions. The mechanism of LRV decline by many process streams was proposed to be due to selective plugging of small pores. A theoretical model as well as a predictive equation for LRV decline versus flow decay was derived; experimental results from filtration studies using pore-plugging feed stocks were consistent with the equation. As protein solutions may vary in their adsorptive versus plugging behaviour during filtration, an evaluation of the LRV-versus-flow-decay relationship on a biopharmaceutical-product-specific basis may be warranted.