A 44-year-old man was diagnosed with cutaneous T-cell lymphoma characterized by a proliferation of CD4-positive cells. In response to alpha-interferon therapy, he experienced rapid regression of his cutaneous disease. This improvement was associated with development of renal failure, characterized by nephrotic-range proteinuria with interstitial nephritis and minimal-change nephropathy. The remarkable finding of renal biopsy was marked proliferation of visceral epithelial cells (podocytes). Renal disease improved significantly in response to discontinuation of interferon and initiation of prednisone therapy. Nephrotic range proteinuria regressed, but never completely resolved. This case is illustrative of the probable role for lymphokine-mediated nephrotoxicity in the setting of lymphoproliferative disease.