The regional distribution of albumin in serum extravasations of cerebral edema was visualized on intact brain slices by autoradiography of 125I-labeled antibodies directed against albumin. Following autoradiographic imaging of edema protein spread, concentrations of total serum proteins were determined by radioimmunoassay in tissue micro samples taken from various regions of the brain. Peptide fragments of albumin--produced upon proteolytic breakdown of the native protein in vivo--were separated by affinity chromatography and HPLC. The combination of techniques for imaging, direct quantification, and analysis of molecular structure of serum proteins was provided to be valid in three different types of experimental cerebral edema in the rat: cortical cryogenic lesion, brain tumors, and stroke-prone spontaneous hypertension. The results indicate differences in the reactivity of edematous tissue with respect to proteolytic activity, depending on the susceptibility of serum proteins to in vivo fragmentation.