Experimental evidence suggests a pathogenetic role for lipids in focal glomerulosclerosis (FGS) analogous to atherosclerosis. As foam cells (FC) are an important factor in atherosclerosis, a retrospective comparative study was done to evaluate the significance of intraglomerular FC in human FGS. Glomerular FC infiltration was evaluated in 115 biopsies of FGS, 120 biopsies of membranous glomerulonephritis (MGN) and 50 biopsies of minimal-change disease (MCD). Selected clinical and laboratory data collected at about the time of biopsy were reviewed. The proportion of biopsies showing glomerular FC was much higher in FGS (70%) than in either MGN (12%) or MCD (0%) p < 0.001. The mean percent ( ± SD) of glomeruli with FC per biopsy was significantly greater in FGS (7.9 ± 9.9) than in MGN (2.0 ± 7.8; p < 0.0001). Of the 14 MGN biopsies with FC, 13 showed superimposed FGS. Mean serum total cholesterol and triglyceride were not significantly higher in FGS than in either MGN or MCD. The results demonstrate a close association of glomerular FC infiltration with F