The separation of patients with idiopathic nephrotic syndrome into those with lipoid nephrosis and membranous nephropathy on the basis of ultrastructural study of renal biopsy material is supported by contrasts in the natural history and response to therapy of the groups. Nineteen patients with the latter lesion have been followed for periods of up to eleven years. Nine are known to have expired with a mean duration of clinical illness of six years. Nine survivors are known with a mean duration of clinical illness of 5.3 years. Corticosteroid therapy rarely appears to provide sustained clinical improvement. However, remissions with loss of clinical features of the illness have been observed in five patients. Serial renal biopsies indicate the morphologic lesion is usually unchanged or progressive, despite subsidence of proteinuria and clinical remission. In one patient a renal biopsy in her third year of remission showed striking regression of a previously marked membranous change. Morphologic differentiation from renal involvement with systemic lupus erythematosus may be difficult and diagnosis depends on evidence of multisystem disease and additional laboratory studies. Review of reported immunofluorescent studies of biopsy material and comparison with experimental lesions suggest the glomerular membranous lesion is immunologically determined.