Familial lecithin cholesterol acyltransferase (LCAT) deficiency is a rare inherited enzyme deficiency characterized by widespread disturbance of lipid metabolism and infiltration of many organs, including kidneys by lipids; usually it results in death from renal failure in the fourth or fifth decades. We have described a new family with LCAT deficiency and have studied three sisters with characteristic corneal opacities and no detectable plasma LCAT activity, together with eight obligate heterozygotes who have reduced LCAT activity but are phenotypically normal. All three sisters had the typical lipid abnormalities including large molecular weight particles in the low density lipoprotein (LDL) fraction of plasma previously described only in LCAT deficient patients with renal disease. However, only the youngest sister had proteinuria and renal failure. Renal biopsies from two of the sisters were infiltrated with lipid but the biopsy from the youngest contained electron dense deposits indistinguishable from those seen in immune complex disease. These findings cast doubt on the concept that large molecular weight LDL particles are the sole determinants of renal failure in LCAT deficiency.