A 23-year-old black female presented with general malaise, headache, high white cell count (136 x 10(9)/L), thrombocytopenia and nephrotic syndrome. She proved to have large granular lymphoproliferative disease with a natural killer cell phenotype and without a clonal rearrangement of the T-cell receptor genes. Renal biopsy demonstrated focal segmental glomerulosclerosis (FSGS). She developed a monophasic neurological illness, and rapidly became comatose six days after the initiation of high dose prednisone therapy. Computerized tomography of the brain showed marked hypodensity of the subcortical white matter. She regained consciousness subsequently, but died six months after her initial presentation with uncontrolled lymphocytosis and renal failure. Autopsy revealed FSGS with glomerular collapse and microcystic dilatation of the renal tubules, and there was perivascular demyelination in the subcortical white matter of the brain. We speculate that lymphokines released by the natural killer cells may have played an important role in the pathogenesis of both the nephrotic syndrome and leukoencephalopathy.