One hundred and twenty-nine dogs with pituitary-dependent hyperadrenocorticism were treated according to a protocol aimed at the complete destruction of the adrenal cortices by the administration of O,p'-DDD (mitotane) at a daily dose of 50 to 75 mg/kg bodyweight for 25 days. On the third day, glucocorticoid and mineralocorticoid supplementation was begun for the induced adrenocortical insufficiency. The first follow-up examination after completion of the 25-day course and the subsequent twice-yearly follow-up examinations included physical examination and measurements of plasma concentrations of sodium and potassium to optimise substitution therapy. In 19 dogs the full course of 25 days treatment could not be completed. Of the 110 dogs which received the full course of treatment, the administration had to be stopped temporarily in 32 because of side-effects, such as anorexia and vomiting. The actual dose of o,p'-DDD administered was not significantly different in the dogs with and without these side-effects. Clinical remission occurred in 111 dogs (86 per cent), of which 43 (39 per cent) had a relapse. The estimated one-year disease-free fraction was 77 per cent (95 per cent confidence interval [CI]: 67 to 85 per cent). The estimated one-year survival fraction was 80 per cent (95 per cent ci: 71 to 87 per cent), the two-year survival was 69 per cent (95 per cent ci: 59 to 78 per cent), and the three-year survival was 61 per cent (95 per cent CI: 49 to 71 per cent). The bodyweight and age of the dogs and vomiting occurring during the period of treatment, were positively correlated with the length of the disease-free period, whereas weakness during the treatment and resistance to dexamethasone suppression of the urinary corticoid/creatinine ratios at the start of the treatment were associated with a relatively short survival time.