With a view to elucidating the physiologic role of hepatic triglyceride lipase (H-TGL), we studied the relationship between the activity of H-TGL and the concentrations of the lipids of ultracentrifugally separated lipoprotein fractions in sera from 81 cases of primary hyperlipidemia, 5 of hypothyroidism, and 31 normal subjects. The activity of H-TGL in postheparin plasma was determined by the sensitive, nonradioisotopic method that was recently developed by us. In the entire group of subjects including the normals, the activity of H-TGL had a significant inverse correlation with the concentration of the cholesterol (r = -0.443, P less than 0.001) and phospholipid (r = -0.433, P less than 0.001) of intermediate density lipoprotein (IDL). When the patients were divided into subgroups according to the phenotype of hyperlipidemia, it was found that the correlation was more significant in type IIb (r = 0.695, P less than 0.001) or type IV + V (r = -0.664, P less than 0.0001). In the five cases of hypothyroidism, the mean IDL cholesterol level was high (28.3 +/- 12.3 mg/dL) and the H-TGL activity was very low (4.6 +/- 4.5 mumol/h/mL). The H-TGL activity was also significantly correlated with the ratio of high density lipoprotein-2 to high density lipoprotein-3 cholesterol (r = 0.351, P less than 0.001) in the entire group.(ABSTRACT TRUNCATED AT 250 WORDS)