We have observed the occurrence of focal segmental glomerulosclerosis in all three siblings of a single Hispanic family. Each of the children had the onset of significant proteinuria on or before the age of 10. The two oldest children have had progression of their disease to end-stage with subsequent successful transplantation. The youngest sibling continues to have normal renal function. All three patients had renal biopsies prior to the onset of renal insufficiency and each of the biopsies showed the presence of focal segmental glomerulosclerosis with mild diffuse mesangial hypercellularity. Finally, HLA-typing revealed the presence of DRw8 in all three siblings and the father. This report further suggests that genetic factors may be quite important in the development of the lesion of focal segmental glomerulosclerosis.