Adsorption and desorption of human serum albumin (HSA) from aqueous solutions on mica were studied using AFM and in situ streaming potential measurements. A quantitative interpretation of these experiments was achieved in terms of the theoretical model postulating a 3D adsorption of HSA molecules as discrete particles. These measurements, performed for various ionic strength, allowed one to determine the coverage of HSA as a function of the zeta potential of mica. This allowed one to determine the amount of irreversibly bound HSA as a function of the ionic strength. It was found that the coverage of irreversibly adsorbed HSA increased from 0.52 mg m(-2) for I = 1.3 x 10(-3) M to 1.6 mg m(-2) for I = 0.15 M (pH = 3.5). The significant role of ionic strength was attributed to the lateral electrostatic repulsion among adsorbed HSA molecules, positively charged at this pH value. This was quantitatively interpreted in terms of the effective hard particle concept previously used for colloid particles. The experimental results confirmed that monolayers of irreversibly bound HSA of a well-controlled coverage can be produced by adjusting the ionic strength of the suspension. (C) 2011 Elsevier Inc. All rights reserved.