The activity of lipoprotein lipase (E.C.3.1.1.3) extracted and released from adipose tissue has been measured in obese subjects with mild or severe hypertriglyceridaemia. The Intralipid tolerance test has been studied as a measure of in vivo clearance of exogenous triglyceride from plasma. 2. Plasma triglyceride clearance was reduced in patients with severe hypertriglyceridaemia (> 4 mmol/l) and this was associated with reduced activities of extracted lipoprotein lipase in adipose tissue compared to patients with mild hypertriglyceridaemia (2--4 mmol/l). 3. A course of insulin therapy (20 u/day) for 1 week increased the extracted, but not the released component of the enzyme from adipose tissue of hypertriglyceridaemic patients. 4. Serum (25% v/v) potentiated the release of lipoprotein lipase from adipose tissue of normo- but not hypertriglyceridaemic patients. 5. The effect of serum on enzyme release was abolished if lipoprotein-deficient serum was used. Addition of very low density lipoprotein (VLDL) or high density lipoprotein (HDL) restored the ability of delipidated serum to augment release of enzyme from adipose tissue, but this was not observed with low density lipoprotein (LDL). 6. It is suggested that a defect in the release of lipoprotein lipase activity in adipose tissue may contribute to the development of hypertriglyceridaemia in this group of patients.