The renal filtration, absorption and final disposal of lysozyme (lysozyme--mol wt 14,000), insulin and growth hormone were studied to gain a better quantitative understanding of the fundamental variables involved in the renal handling of low molecular weight proteins. The glomerular barrier offers little hindrance to the filtration of lysozyme, the glomerular sieving coefficient being 0.8 plus or minus 0.1 (SD). The intrarenal route by which injected lysozyme accumulates in the kidney is via filtration and subsequent absorption (uptake) by renal tubular cells. Uptake or adsorption from the peritubular side is negligible compared to luminal uptake. Renal clearance and renal titration experiments in the intact dog and in the isolated perfused rat kidney showed that the lysozyme absorption process can be best characterized as high capacity, low affinity transport system which is directly or indirectly dependent on energy input. The final disposal of absorbed 125I-lysozyme, 125I-insulin and 125I-growth hormone was studied in the isolated perfused rat kidney by measuring the radioactivity by gel chromatography. The rate of release of radioactivity as well as its nature was dependent on the molecular species of the absorbed protein. The rate of release was higher for 125I-insulin and 125I-growth hormone and lower for 125I-lysozyme. Lysozyme absorbed from the luminal side was released to the perfusate both as intact protein molecules and as catabolic products, whereas absorbed 125I-insulin was almost entirely released to the perfusate as catabolic products. It is concluded that low molecular weight proteins are extensively filtered by the kidney, absorbed from the luminal side by renal tubular cells and released back to the circulation either as intact molecules or as catabolic products (amino acids and polypeptides). This process contributes in an important way to the plasma turn-over of low molecular weight proteins including peptides and proteins hormones.