Plasma lipoproteins from patients with familial lecithin:cholesterol acyltransferase (LCAT) deficiency have been fractioned by preparative ultra-centrifugation and gel filtration and their lipid content and reactivity studied. All of the lipoproteins are abnormal with respect to lipid concentration or relative lipid content. The low density lipoproteins (LDL) and high density lipoproteins (HDL) appear to react normally with partially purified LCAT from normal plasma. Also, the lipids of the very low density lipoproteins (VLDL) and LDL, like those of the corresponding lipoproteins of normal plasma, are indirectly altered by the action of LCAT on normal HDL. Thus, during incubation in vitro VLDL cholesteryl ester is increased and VLDL triglyceride is decreased, as described by others for VLDL from hyperlipemic plasma, and both the unesterified cholesterol and lecithin of the VLDL and LDL are decreased. The patients' VLDL and LDL are abnormal, however, in that they lose unesterified cholesterol and lecithin to normal HDL in the absence of LCAT. Also, the patients' HDL lose these lipids to erythrocyte membranes in the absence of the enzyme.