A case of nephrotic syndrome and acute renal failure in a 74-year-old man with latent syphilis is described. A renal biopsy demonstrated focal global sclerosis in three of nine glomeruli, however, the remaining glomeruli revealed typical lesions of minimal change disease. Previous reports of renal involvement in syphilis have described membranous glomerulonephritis, mesangial and endothelial cell proliferative glomerulonephritis, and, recently, rapidly progressive glomerulonephritis. The proteinuria and renal failure resolved after penicillin therapy alone. This response strongly suggested that there was a causal relationship between the syphilis and the nephrotic syndrome. This is the first report of such a relationship. © 1987, National Kidney Foundation, Inc.. All rights reserved.