A review of all native kidney biopsies at our center from 1974 to 1993 identified 43 cases of idiopathic focal segmental glomerulosclerosis (FSGS) with predominantly collapsing features and lacking evidence of HIV-1 infection or intravenous drug use. No case was identified before 1979 and the incidence of this entity has progressively increased over the past two decades. Compared to 50 age-matched controls of idiopathic FSGS with typical perihilar scars, the group of idiopathic collapsing FSGS displayed black racial predominance, a higher serum creatinine and more severe features of nephrotic syndrome at biopsy. Morphologic features of visceral epithelial cell hypertrophy and hyperplasia, tubular microcysts, tubular epithelial degenerative and regenerative features and interstitial edema were more prevalent and severe in collapsing FSGS. Median time to ESRD was rapid in collapsing FSGS versus controls (13.0 months vs. 62.5 months, P < 0.05). Correlates of progression to ESRD included a higher initial serum creatinine and failure to undergo remission of proteinuria. Both glomerulosclerosis and certain features of tubular damage were independent predictors of the level of renal function at time of biopsy, but not of the rate of progression of renal insufficiency. Although three patients had partial or complete spontaneous remissions, none of 26 patients treated with steroids alone responded. Idiopathic collapsing FSGS is a variant of FSGS with increasing incidence, distinct clinicopathologic features, black racial predominance, a rapidly progressive course and relative steroid resistance.