The effects of trilostane, a 3β-hydroxysteroid dehydrogenase inhibitor on basal cortisol concentrations and the results of acth stimulation tests in dogs with pituitary-dependent hyperadrenocorticism were investigated. In eight of nine dogs trilostane suppressed the concentration of cortisol below the lower limit of the reference range (<50 nmol/l) for a mean (sd) of 3·5 (2·3) hours during the day, but for no longer than 13 hours. In another 10 dogs, there was a clear difference between the post acth cortisol concentrations observed four and 24 hours after the administration of trilostane. Furthermore, in the six dogs whose clinical signs were poorly controlled the post-acth concentrations observed four and 24 hours after the administration of trilostane were always higher than the equivalent cortisol concentrations in the four dogs whose clinical signs were controlled. A short duration of drug action may be responsible for the failure of some dogs to respond adequately to once daily trilostane administration.