The present study is a prospective evaluation of 151 patients with the nephrotic syndrome in regard to the incidence of renal vein thrombosis, modes of clinical presentation, pathogenetic course and response to anticoagulant therapy. Of the 151 nephrotic patients studied, 33 had renal vein thrombosis and membranous nephropathy was present in 20. There were two modes of clinical presentation: (1) a sudden renal vein thrombosis was observed in the young patient with acute flank pain, marked costovertebral angle tenderness and macroscopic hematuria; a characteristic intravenous pyelogram, renal histologic changes and anticoagulant therapy were followed by marked improvement in renal function; (2) long-term renal vein thrombosis was observed in the older patients; they were asymptomatic and intravenous pyelograms disclosed no abnormalities; there were no suggestive renal histologic findings; the incidence of thromboembolic phenomena other than renal vein thrombosis was high, and there was mild progressive deterioration of renal function which was not altered by anticoagulant drugs; treated nephrotic patients with chronic renal vein thrombosis did not experience a new episode of thromboembolism whereas untreated nephrotic patients without renal vein thrombosis did. Finally, the sequence of nephrotic syndrome leading to renal vein thrombosis was clearly established showing the pathogenetic role of the nephrotic syndrome in renal vein thrombosis. Possible mechanisms in the pathogenesis of renal vein thrombosis are also discussed.