Calcium-oxalate nephrolithiasis is associated with a defect in erythrocyte oxalate self-exchange and an abnormal rate of erythrocyte membrane protein phosphorylation. There is evidence that glycosaminoglycans (GAGs) have a regulatory effect on both of these processes. This study tested the hypothesis that modifications of erythrocyte oxalate self-exchange induced by oral GAGs are paralelled by similar changes in overall oxalate metabolism. 40 patients with idiopathic calcium-oxalate nephrolithiasis were treated for 15 days with 60 mg/day of a mixture of GAGs. By day 15 of treatment there were significant reductions from baseline in erythrocyte oxalate self-exchange (mean [SD] 16·7 [1·18] vs 2·59 [1·63] × 102 per min; p<0·005) and erythrocyte membrane protein phosphorylation (55·8 [7·3] vs 72·9 [6·8] × 10-3 cpm/mg protein; p<0·005), but also in urinary oxalate excretion (0·24 [0·09] vs 0·31 [0·15] mmol/24 h; p < 0·005). This finding suggests similar changes in both erythrocytes and other cells more important in oxalate handling. The changes had reversed by 15 days after withdrawal of treatment. Acute intravenous administration of GAGs (60 mg) induced a fall in carbon-14-labelled oxalate renal clearance (143 [13] vs 169 [28] ml/min; p < 0·005), which strongly suggests the participation of the kidney. However, reduced oxalate absorption from the intestine, and even decreased synthesis of oxalate, cannot be ruled out.