Using binephrectomized anaesthetized rats, we explored the possibility that calcium antagonists may alter the partition of extracellular fluid between plasma and the interstitium, as suggested for atrial natriuretic factor (ANF). The effects of intravenous infusion of synthetic ANF (103-126 ANP; Wy 47.663) and the dihydropyridine derivative nicardipine were assessed by measuring changes in haematocrit and plasma proteins. After a 40-min infusion of ANF or nicardipine, haematocrit increased significantly (9% and 5.4%, respectively). The calculated loss of plasma volume was 15% after administration of ANF and 9.1% after nicardipine compared with 3.9% in rats receiving vehicle only. Plasma proteins increased by only 3.9% (after ANF) and 3.7% (after nicardipine), less than expected for a plasma volume contraction without protein extravasation. Atrial natriuretic factor and nicardipine induced a similarly slight change in mean arterial pressure. These results suggest that nicardipine and ANF both reduce plasma volume by an extrarenal mechanism; part of the fluid shift might be facilitated by an increased vascular permeability to proteins.