To determine the site of degradation of human placental lactogen (HPL) the disappearance rate of 125I-labelled and unlabelled HPL was studied in intact normal and nephrectomized dogs. Methods for determining plasma levels of 125I-labelled HPL included measurement of total radioactivities, radioactivities after trichloroacetic acid precipitation and immunoprecipitation, and chromatoelectrophoresis. Plasma HPL levels were determined by a radioimmunoassay method. In the dog, of the several organs studied, only the kidney was found to be involved in the degradation of both labelled and unlabelled hormone. The role of the kidney in the degradation of polypeptide hormones is discussed.