Two patients on long-term lithium therapy developed the nephrotic syndrome. Ultrastructural study of a renal biopsy in each case showed extensive glomerular epithelial cell foot process fusion. Lithium was withdrawn in each case. The nephrotic syndrome cleared without steroid therapy and has not recurred 18 months later in one patient. The other patient required a further course of treatment with lithium and the nephrotic syndrome returned. Further biopsy revealed a more severe glomerular lesion. The nephrotic syndrome responded again to withdrawal of lithium and institution of steroid therapy. Lithium is known to cause acute renal failure and tubulo-interstitial disease, but the recently described association with proteinuria or nephrotic syndrome is little recognized.