Studies on plasma triglycerides (TG) were performed in 10 nonobese and 16 obese patients with hypothyroidism and in 13 with hyperthyroidism. Nonobese, hypothyroid patients generally had normal levels of TG, but obese patients often had hypertriglyceridemia. In most hypothyroid patients 1-thyroxine treatment lowered plasma TG, and most hyperthyroid patients had low TG. One mechanism whereby thyroid hormones might decrease plasma TG could be to increase lipoprotein lipase (LPL). However, post-heparin LPL was not increased after therapy, nor was it increased in hyperthyroid patients. In contrast, hypothyroid patients had abnormally low levels of post-heparin hepatic triglyceride lipase. In hypothyroid patients without hypertriglyceridemia, clearance of chylomicrons was normal. A few obese, hypothyroid patients with fasting hypertriglyceridemia had low clearance of chylomicrons, which may have been due in part to competition for removal of excess endogenous TG. Thus, no evidence was obtained for a significant abnormality in chylomicron metabolism in hypothyroidism. Nonobese, hypothyroid patients had normal synthesis and clearance of very low density lipoprotein (VLDL)-TG. In contrast, VLDL-TG synthesis was increased in 8 obese, hypothyroid patients, and fractional clearance rates were relatively low compared to obese, euthyroid subjects. In striking contrast, hyperthyroid patients had remarkable facility in clearing VLDL-TG. Thus, TG metabolism is not grossly deranged in hypothyroidism, but thyroid hormones apparently can promote catabolism of VLDL.