Therapeutic use of amiodarone (AD), an effective antiarrhythmic drug, is associated with serious pulmonary toxicity (e.g., fibrosis and phospholipidosis). In the present study, we tested if taurine and/or niacin, which prevent bleomycin-induced lung toxicity, could prevent AD-induced lung toxicity in hamsters. AD alone significantly increased lung hydroxyproline (an index of fibrosis) and lung phospholipid (an index of phospholipidosis) levels to 154 and 133% of their control counterparts at 21 days, respectively. However, treatment of hamsters with taurine, niacin or taurine + niacin for 6 days before AD, and daily thereafter, significantly decreased subsequent AD-induced collagen accumulation. Similarly, phospholipid levels in niacin + AD and taurine + niacin + AD groups were decreased significantly compared to AD alone. We conclude that taurine and niacin administered p.o. either singly or in combination can significantly decrease AD-induced increases in lung collagen deposition and phospholipidosis and may, therefore, be potentially useful in reducing AD-induced pulmonary toxicity.