Besides suppressing sebum production, the exact mechanism of action of isotretinoin in acne vulgaris is not known. Several hormones have been linked to the pathogenesis of acne. In this study, we investigated the effects of isotretinoin on the pituitary-adrenal axis, whose activity may be increased in acne. Various hormone systems were evaluated before and after 3 months of isotretinoin treatment in 47 acne patients. Free triiodothyronine (T3), thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibody levels decreased significantly during isotretinoin treatment (p < 0.001, p < 0.02 and p < 0.02, respectively), as did those of luteinising hormone, prolactin and total testosterone (p < 0.005), as well as morning cortisol and adrenocorticotropic hormone (p < 0.005 and p < 0.05, respectively). We conclude that isotretinoin causes mild suppression of pituitary hormone levels, which may be beneficial for tackling the pathogenesis of acne.