1. Intraortic suprarenal infusion in vivo of New Zealand White rabbits with plasma from patients with the nephrotic syndrome reduced the number of anionic sites labelled by the cationic polymer polyethyleneimine in the lamina rara iterna to 14.0 +/- 2.7 per 1000 nm of lamina rara interna (mean +/- SD) compared with 18.7 +/- 2.1 (P less than 0.005) after infusion of plasma from normal subjects. 2. Proteinuria increased in all nine animals infused with nephrotic plasma and in two of seven infused with control plasma (P less than 0.01). The mean increase in proteinuria in the animals infused with nephrotic plasma was 246 mg/l (P less than 0.05), whereas in those infused with control plasma there was no increase. 3. We conclude that nephrotic plasma contains a factor(s) capable of neutralizing the charge of these anionic sites and concomitantly increasing proteinuria.