The dorsal subcutaneous injection in rats of 12 ml or more of autologous hemolyzed whole blood clotted in situ induced the formation of sterile, hemispheric lesions, 47% of which showed an initial decrease in volume followed by a progressive enlargement. The behavior, histology, and biochemical characteristics of the liquid contents of these lesions were found to be remarkably similar to those of subdural hematomas in man. To evaluate the role of the various blood components that may have influenced the formation and growth of these lesions, more than 150 clots composed of human platelet-free plasma, autologous hemolyzed blood, or autologous whole blood were implanted subcutaneously in rats by either surgical or injection techniques. The in vitro behavior of the different clots used was also assessed. This systematic approach led to the following conclusions: 1) the composition and volumes of the clots are critical variables; 2) plasma-fibrin provides the matrix shape of the lesions; 3) the breakdown products derived from erythrocytes, hemoglobin, leukocytes, and other solid blood elements induce neomembrane formation and contribute to the lesion's subsequent growth; and 4) inflammation mechanisms appear to be essential, while cerebrospinal fluid plays no discernable role in this process.