Fourteen normal dogs received continuous infusions of intravenous heparin for one year by means of an implantable infusion pump. Heparin wad admistered at an overall mean rate of 666 units/kg/day, a dose sufficient to prolong the Lee-White clotting time to greater than twice normal. Eight control, animals, under the same dietary and activity regimen, received continuous infusions of bacteriostatic water for one year by means of implanted pumps. Serum cholesterol concentrations rose to 50% above control values after one month of heparin infusion, and remained significantly (P less than 0.05) elevated at this level for the remaining 11 months. Serum triglyceride levels were unchanged. A possible mechanism for this elevation resides in the known effect of heparin to increase plasma free fatty acid concentrations by its activation of lipoprotein lipase. These results may have implications for the long-term use of heparin anticoagulation in the treatment of atherosclerotic states in man.