The understanding of the structural and thermodynamic properties of moderately or highly concentrated solutions is fundamental, e.g., in medicine and biology and also in many technical processes, In this work, we have used the small-angle neutron scattering method (SANS), in combination with Monte Carlo simulation, to study salt-free solutions of human serum albumin (HSA) in the concentration range up to 0.26 g ml(-1). The model calculations of the theoretical SANS intensities are quite general, thus avoiding the approximation that the relative positions and orientations of the particles are independent of each other. The computation of the theoretical intensities also includes the calculation of a 'thermodynamic' intensity scattered at zero angle, which is obtained via the nonideal part of the chemical potential. The latter quantity is obtained by applying the test particle method during the Monte Carlo simulations. It is found that the SANS data can be explained by a model where the HSA molecules behave as hard ellipsoids of revolution with semiaxes a = 6.8 nm, b = c = 1.9 nm. In addition to the hard core interaction, the particles are also surrounded by a soft, repulsive rectangular-shaped potential which is spherically oriented around the particles. The combination of SANS and statistical thermodynamics also allows a determination of the nonideal part of the chemical potential and the activity coefficient of HSA. As expected the activity coefficient deviates strongly from the value one (several powers of ten) already at fairly low concentrations; the effects are comparable to, or even larger than, for instance hydrophobic or van der Waals interaction. (C) 1997 Elsevier Science B.V.