This study was designed to characterize the effect of urinary sodium excretion on amino acid excretion in cystinuria. We studied three homozygous patients with cystinuria at various levels of sodium intake ranging between 50 and 230 mmol/day. A reduction in sodium intake produced a marked decrease in rates of urinary cystine excretion. The low-sodium diet also reduced the excretion of lysine but had no significant effect on the excretion of ornithine or arginine. We conclude that a dietary restriction of sodium may reduce the urinary excretion of cystine and can provide a simple and safe long-term approach to the treatment of cystinuria.