Glucocorticoid replacement therapy should be tailored to individual patients' requirements to avoid the risks of over and under treatment. Serum and urinary free cortisol profiles over 24 hours were compared as a means of assessing replacement therapy in nine patients on long-term twice daily hydrocortisone. Both indices varied in relationship to the timing and dose of hydrocortisone and there was a close correlation between individual measurements of serum and urinary free cortisol (r = 0.885, p < 0.0001). Collection of urine samples offers certain advantages over repeated serum sampling and urinary free cortisol measurement may have a role in the assessment of hydrocortisone replacement therapy.