SummaryThis study was designed to investigate the greatly reduced activities of hepatic lipase and lipoprotein lipase in postheparin plasma of patients with glycogen storage disease (GSD). Evidence for the presence of a circulating inhibitor in the plasma of GSD patients prior to the establishment of metabolic control was provided by the following observations.The hepatic lipase activity from patients with GSD gave a nonlinear relationship with time, maximum activity being obtained after 5 min whereas normal postheparin plasma showed a linear relationship for at least 20 min. The addition of GSD plasma to a normal postheparin plasma resulted in inhibition of the normal postheparin lipolytic activity. The inhibition showed a dose response, with 10 and 30 µl of the GSD plasma giving 22 and 65% inhibition after 20 min, respectively. Serial dilution of GSD postheparin plasma gave increasing activity of hepatic lipase when expressed per ml of plasma. Thus, a 1:100 dilution gave a normal activity of 15 µmol/ml/h whereas a 1:10 dilution gave less than 10% of this activity. After affinity chromatography of the GSD postheparin plasma on heparin/Sepharose, the inhibition was removed and a normal lipolytic activity was obtained.