Studies of 117 patients on long-term sodium heparin therapy disclosed cumulative evidence of a relationship between prolonged use of large amounts of heparin and osteoporosis. No symptoms of osteoporosis developed in 107 who received 10,000 units of concentrated sodium heparin once daily or less for 1 to 15 years. Of ten treated daily with larger doses (15,000 to 30,000 units) for six months or longer, spontaneous fractures of vertebrae or ribs developed in six, and biopsies disclosed soft, bony matrix. Studies of rats on sufficient heparin therapy to triple clotting for ten days indicated that collagenolytic activity of rat-bone-cell homogenate increased two to four times, and the stability of the lysosome-like bodies in bone cells which contain collagenase appears to be decreased. If these observations are true, hyperheparin states, whether spontaneous or man-induced, may take their place in the small growing category of lysosomal diseases.