A life span study with 900 female virgin Han:NMRI mice (300 outbred controls, 300 of a fat subline and 300 of a lean subline) was carried out to determine the occurrence of spontaneous disease with ad libitum or restricted feeding. The major age-dependent non-neoplastic alteration of the thyroid was a cystic distension of the ultimobranchial bodies (up to 90% in the oldest age groups). Most of the severely cystic thyroids were found in animals of the fat sublines and development seemed to be slightly delayed by food restriction. The cyst walls were composed of ciliated and non-ciliated granular or highly attenuated cells. The cysts contained Alcian blue and periodic acid Schiff positive substances.