Protein transport in the extracapillary and intracapillary spaces (ECS and ICS) as well as across the membranes of hollow-fibre devices was investigated. Regenerated-cellulose ultrafiltration membrane cartridges were loaded with solutions of myoglobin and operated in the closed-shell mode for a period of several days. The transmembrane leakage and spatial distribution of myoglobin were dependent on the protein loading, the ICS flow rate and the presence of bovine serum albumin in the ECS. A mathematical model was developed to characterise the time-dependent protein redistribution, taking into account the effects of osmotic pressure, fibre expansion under wet conditions and the fibre-free manifold regions of the ECS. According to the model, the transmembrane transport of protein can be described using one semi-empirical parameter, the membrane constant, defined as the ratio of the square of pore tortuosity to surface porosity, from which the osmotic reflection coefficient, the partition coefficient, and the diffusive and convective hindrance factors can be calculated. The experimental data were used to test the model and to find the values of the membrane constant for the system under consideration.