The turnover of 125I labelled rat polymorphonuclear leukocyte (PMN) cathepsin G with retained enzymatic activity was followed 180 min after an intravenous injection. The plasma half-life of injected radioactivity was approximately 4.5 min. In the plasma sample 15 min after injection the main part of the radioactivity in a gel filtration eluted at the same volume as 3-iodo-tyrosine (3-IT). After 15 min the liver contained about one third of the injected radioactivity. Radioactivity in all organs declined in the course of time. In the pancreas autoradiography showed labelling at the localization of enzyme granules as soon as 15 min after the intravenous injection of radiolabelled substance. All these results suggest a rapid uptake and degradation of cathepsin G in the liver. The distribution of cathepsin G in tissues analysed in the normal rat were localized to the spleen, lymph nodes, and lung. PMNs were immunohistochemically stained, while in the lung indefinable epithelial cells were stained. When rat PMN cathepsin G was added to normal rat plasma, we could identify 36% bound to alpha 1-macroglobulin (alpha 1M) and 19% bound to alpha 1-inhibitor 3 (alpha 1I3) as judged from analysis of gel filtration chromatography and electroimmunoassay (EIA) with autoradiography.