Seven salt depleted patients with the idiopathic nephrotic syndrome were treated with various non-steroidal anti-inflammatory drugs. Indomethacin, diclofenac-sodium and flurbiprofen decreased proteinuria, glomerular filtration rate, plasma renin activity and renal prostaglandin E2 excretion by 59%, 19%, 55% and 68% respectively. Sulindac induced no major changes in proteinuria, glomerular filtration rate, plasma renin activity and renal prostaglandin E2 excretion. The relative change in proteinuria and glomerular filtration rate during non-steroidal anti-inflammatory drug treatment correlated strongly with that of the renal prostaglandin E2 excretion (r = 0.89 and r = 0.70, respectively p less than 0.05). It is likely that the anti-proteinuric effect of non-steroidal anti-inflammatory drugs is dependent on their potency to inhibit renal prostaglandin synthesis and it is suggested that this effect is mediated by lowering transcapillary glomerular hydraulic pressure.