Three distinct genotypes of mice with vasopressin-resistant urinary concentrating defects are compared to a normal strain with respect to urine volume and osmolality, serum osmolality, and sizes of supraoptic (SON) and paraventricular (PVN) neurons and the various parts of the pituitary gland. Mice with severe diabetes insipidus (DI) produce large volumes of dilute urine; their hypertrophied SON and PVN cells have markedly enlarged nucleoli; the pars nervosa (which stores ample amounts of neurosecretory material), the pars distalis and the pars intermedia are all larger than normal, the latter exhibiting the greatest relative increase in size. The two mouse strains with “mild DI” occupy intermediate positions in most of the above parameters suggesting an interrelationship between the amount of fluid turnover and the degree of hypertrophy. Additionally, the results suggest that there may be a relationship between increased neurohypophyseal activity and the hypertrophy of the pars intermedia.