Treatment with desoxycorticosterone acetate (DOCA) and 1 per cent saline as drinking water for 21 days caused a significant and similar increase in blood pressure in haired mice, with a normal thymus function, as in nude mice with genetical aplasia of the thymus. After 57 and 78 days there was, however, a significantly more pronounced increase in blood pressure in haired than in nude mice. A marked degree of round cell infiltration around intrarenal vessels and degenerative changes including wedge-shaped infarcts were observed in the kidneys of the haired mice, commencing after 57 days of treatment, while no such changes were found in nude mice. Thymus grafting in nude mice, successively treated with DOCA and salt, conferred the ability to react with chronic hypertension and intrarenal vascular disease, equal to the reaction seen in haired mice. The present investigation has provided evidence for the existence of an initial thymus independent and a chronic thymus dependent phase of DOCA and salt hypertension in mice. It still remains an unsolved problem whether the secondary blood pressure fall observed in nude athymic mice is a direct consequence of the lack of perivascular cellular immune reactions, or caused by other defects in this strain of mice.