Patients with primary hypertriglyceridemia have been reported to manifest increased in vivo turnover of plasma cholesteryl esters. To ascertain if this is due to plasma lecithin:cholesterol acyltransferase (LCAT) and to explore a possible link between triglyceride and cholesteryl ester turnover, we have measured LCAT in 15 patients with Type IV, 2 with Type V, 1 with Type III, and 9 with Type II B hyperlipoproteinemia. LCAT was significantly elevated (p less than 0.001) in hypertriglyceridemic subjects, regardless of lipoprotein pattern. In the Type IV group, but not in normal subjects, LCAT correlated significantly with measures of very low-density lipoprotein (VLDL) elevation, including plasma triglycerides and particularly VLDL-unesterified cholesterol, but not with body weight or substrate high-density lipoprotein (HDL) lipid levels. On repeated determinations in individual subjects, a relationship between triglyceride fluctuations and LCAT could be demonstrated in only one subject over an extreme range of triglyceride levels. Analysis of lipoprotein lipids revealed that the ester:free cholesterol ratio in VLDL was increased in hypertriglyceridemia, but was not correlated with enzyme level. In vitro removal of endogenous VLDL or addition of VLDL from lipemic plasmas to normal plasmas was without effect on enzyme activity. Regulation of enzyme activity does not appear to be a direct function of VLDL level.