One of the major complications of glucocorticoid treatment is bone loss. 21-Hydroxylase deficiency is the most frequent inborn error of steroidogenesis, leading to congenital adrenal hyperplasia (CAH): synthesis of cortisol is impaired and replacement therapy is therefore mandatory. We studied the bone mineral density in a group of patients with congenital adrenal hyperplasia (CAH) on long-term glucocorticoid replacement therapy. We selected 30 Caucasian patients with CAH due to 21-hydroxylase deficiency (mean +/- SD age = 17.45 +/- 2.49 years). 22 patients had the classical CAH form and the remaining 8 had the nonclassical (late-onset) form. The mean duration of therapy was 15.20 +/- 4.04 years. Bone mineral density (BMD) was evaluated with a dual-energy X-ray absorptiometer. BMD was also measured in 73 healthy white volunteers of comparable age (17.35 +/- 2.99 years). BMD values of the spine (sBMD), total body (TBBMD), legs, and arms of CAH patients, adjusted for confounding variables (age, gender, body mass index), did not differ from those of control subjects (p = 0.86; p = 0.17; p = 0.06 and p = 0.26, respectively). sBMD and TBBMD values did not show relationships with the duration of treatment and the dose of corticosteroids. Patients with the classical form of CAH had bone density values comparable with those of patients with the nonclassical form (sBMD: p = 0.33; TBBMD: p = 0.97). Our data show that, despite long-term treatment with glucocorticoids, CAH patients have bone density values comparable with controls.