A sensitive enzyme-linked immunosorbent assay for mouse epidermal growth factor was established for measurement of the content of epidermal growth factor in the remaining kidney after uninephrectomy. In 5-week-old male mice, the renal epidermal growth factor content before uninephrectomy was 355±97 ng/g wet tissue with a 2.1-fold increase on the first day after uninephrectomy, whereafter it gradually decreased. In 15-week-old mature male mice, the renal epidermal growth factor content increased 1.7-fold on the first day after uninephrectomy. Immunohistochemical analysis showed that epidermal growth factor was present in the distal tubular cells and that the staining intensity was increased on the first day after uninephrectomy. During the course of compensatory renal growth, no significant alteration of epidermal growth factor content was observed in plasma or in the submaxillary gland. Our data suggest that the increase in renal epidermal growth factor content after uninephrectomy is due to an increased production of epidermal growth factor in the kidney itself. The significance of this phenomenon is discussed.