22 children, with the onset of the nephrotic syndrome between 1 and 6 years of age, were studied by renal biopsy because of steroid resistance or after many years of steroid-sensitive disease. Six children, steroid-resistant from onset or early in the course of disease, had only minimal glomerular changes on both light and electron microscopy. In six children with steroid-sensitive disease, early evidence of sclerosis was present on ultrastructural examination when glomeruli appeared normal on light microscopy. The remaining ten patients, biopsied after 3–17 years of polycyclic steroid-sensitive disease, had focal sclerotic lesions on both light and electron microscopy. These observations demonstrate a broad spectrum of clinicopathological relationships in the nephrotic syndrome of childhood and suggest that in some patients focal glomerulosclerosis may evolve from a minimal change lesio