Background: Adrenal insufficiency following initial treatment of active tuberculosis (TB) is a rare phenomenon. It is also one of the most important causes of mortality within the first few days of TB treatment. The present study evaluated this adverse effect of anti-tuberculous treatment. Materials and Methods: A prospective study was performed on TB patients hospitalized in Masih Daneshvari Hospital between 2004 and 2005. All patients had received standard anti-TB drug regimen. We evaluated pseudo-adrenal insufficiency in these patients. Results: The study group included 429 patients out of which 6(1.4%) developed adrenal insufficiency following anti-TB treatment. In all 6 patients, basal serum cortisol levels were measured which were below the normal range after treatment. No patient had clinical findings of adrenal insufficiency before initiation of anti-TB therapy. After treatment with dexamethasone, the general condition of patients improved. (The average response to treatment was 3.1±1.7 days). No mortality was reported during the treatment course or follow-up period. Conclusion: In TB patients, the adrenal reserve/ serum cortisol reserve level is low. Standard anti-TB drug regimen including rifampicin causes rapid catabolism of cortisol in tissues specially in the liver and lungs; therefore, serum cortisol level will be more decreased and consequently the patient develops adrenal insufficiency. As a whole, despite of the low incidence rate of this adverse effect, early diagnosis and treatment is essential to save the patient's life. (Tanaffos 2007; 6(1): 67-70)