The body distribution of poly(vinyl alcohol) (PVA) with molecular weights (MW) from 14,800 to 434,000 Da was investigated after intravenous administration and compared with that of other water-soluble polymers such as poly(ethylene glycol) (PEG), gelatin, dextran, and pullulan. The half-life of PVA in the circulation was prolonged from 90 min (MW 14,800 Da) to 23 h (MW 434,000 Da), similar to that of PEG which had a half-life of 30 min (MW 6000) and 20 h (MW 170,000). However, the half-life of PVA was much longer than that of other polymers when compared at a similar molecular weight. PVA was located in most organs but with very small accumulation. An insignificant interaction of PVA with cell components, such as macrophages and blood cells, was observed. Similar to PEG, the excretion rate of PVA at the glomeruli was rapidly reduced around 30,000 Da, as the molecular weight increased. These results indicate that the half-life of intravenously injected PVA in the blood was mainly determined by the permeation characteristics of the kidney.