Studies have suggested that lipids participate in the pathogenesis of chronic progressive glomerulosclerosis. To examine the frequency of intraglomerular lipid deposition in routine biopsies, renal biopsy material from 631 consecutive patients with glomerular lesions was studied by light, electron, and immunofluorescence microscopy. Fifty-three patients (8.4%) revealed ultrastructurally detectable lipid deposits in nonsclerotic glomeruli. Seven had minimal lesion, 13 focal-segmental glomerulonephritis, two membranous nephropathy, nine membranoproliferative glomerulosclerosis, 11 IgA nephropathy, and 11 other diseases. Ultrastructurally, the lesion affected small segments of glomeruli, with clusters of lipids which exhibited a heterogenous pattern. A subendothelial accumulation of lipids was observed in 60%, storage of lipids on mesangial matrix in 68%, and intramembranous deposition in 21%. Intracellular accumulation of fat was noted in 23%. Indirect immunofluorescence testing for apolipoprotein B (apo B) and oil red O (ORO) staining were performed in 94 cases. Positive results for apo B and ORO staining in nonsclerotic glomeruli were obtained in 24 patients (26%) and 16 cases (17%), respectively. The distribution of lipids seen in these patients was either in diffuse or focal segmental patterns. The clinical data of 40 patients with glomerular lipid deposition were compared with 80 controls from the residual group of patients matched for age, sex, and disease. Serum creatinine and cholesterol levels, and daily excretion of urinary protein were not significantly different between the two groups. These results suggest that an abnormal accumulation of lipids, mainly of apo B containing lipoprotein, in nonsclerotic glomeruli from routine biopsies is not as rare as previously thought. In addition, factors other than hypercholesterolemia seem to be operative for the glomerular lipid deposition observed in our patients.