Physicochemical effects of hydrated C-60 fullerenes (HyFn) on serum albumin molecules were studied using ESR spin labeling and differential scanning microcalorimetry. Molecular-colloidal solution of hydrated C-60 fullerenes and their small spherical fractal clusters in water (C60FWS), was shown to stabilize protein hydration, and decrease specific surface energy in water-protein matrix in salt solutions. The mechanism of HyFn interaction with protein is discussed in terms of HyFn induced formation of protein clusters and phase transition of hydration water. (C) 2003 Elsevier Science (USA). All rights reserved.