We evaluated the glomerular filtration rate (GFR) in 34 subjects with membranous nephropathy (MN) of new onset. We used physiological techniques to measure GFR, renal plasma flow and oncotic pressure, and computed a value for the 2-kidney ultrafiltration coefficient (K_f). A morphometric analysis of glomeruli in the diagnostic biopsy permitted computation of the single nephron ultrafiltration coefficient (SNK_f). MN subjects were divided into two groups: moderate or severe, according to whether GFR was depressed by less or more than 50%. SNK_f was subnormal, but similar in moderate and severe MN. In contrast, 2-kidney K_f was significantly more depressed in severe than in moderate MN. We estimated the total number of functioning glomeruli (N_g) by dividing 2-kidney K_f by SNK_f. Whereas mean N_g was similar in controls and moderate MN (1.5 and 1.4-1.7 x10⁶, respectively), it was significantly lower in severe MN (0.5x10⁶). This degree of glomerulopenia was not reflected in the rate of global sclerosis. We conclude that a combination of depressed SNK_f (due to foot process broadening) and profound glomerulopenia accounts for GFR depression of >50% early in the course of MN. The cause of the glomerulopenia remains to be elucidated.