The dynamics of fluid volume distribution between the blood and interstitium during hyperproteinemia were studied in 12 anephric, conscious dogs during several states of hydration. After recovery from splenectomy and unilateral nephrectomy, plasma protein concentration was elevated to 8.4-8.7 g/dl by daily intravenous infusion of 330 ml of previously collected autologous plasma for 11 days. The remaining kidney was then removed, and the next day lactated Ringer solution equivalent to 10 or 20% of body weight was infused intravenously. By the end of the 25-h postinfusion period, Ringer infusion had increased circulating protein mass 20.9 ± 9.1% (mean ± SE) in the 10% group (P < 0.05) and decreased it 10.5 ± 3.3% in the 20% group (P < 0.05). The average increase in blood volume and arterial pressure during the postinfusion period was 27.4 ± 2.5 and 20.7 ± 3.7%, respectively, in the 10% group but only 17.8 ± 2.4 and 12 ± 1.6% in the 20% group (all changes significant compared with respective control). The relationship between blood volume and sodium space was similar to that found during normoproteinemia, such that elevations in sodium space of 40-50% increased blood volume but greater elevations in sodium space caused no further increases in blood volume. Overhydration during chronic hyperproteinemia causes hypervolemia and hypertension, but, in contrast to those in short-term studies, the increases in blood volume and arterial pressure are not greater than those achieved during normoproteinemia.