Morphological and biochemical investigations were performed in guinea pigs after 1, 3, 5 and 16 weeks of amiodarone feeding. The most prominent morphological finding was an increase in dense bodies in hepatocytes, Kupffer cells and in bile duct epithelia, reaching a maximum after 5 weeks of treatment according to morphometric analysis. Similar time courses were observed for the serum and liver tissue concentrations of amiodarone and desethylamiodarone and the—albeit minimal—extent of hepatocellular necrosis. Phospholipids in the liver homogenate were unchanged after 1 week, but significantly increased after prolonged amiodarone treatment. There was no significant alteration in the pattern of individual phospholipids. Serum and tissue concentrations as well as the extent of phospholipidosis do not appear to be a function of the duration of drug application. A very close correlation, however, was observed between the liver tissue concentration of amiodarone and the amount of dense bodies as a morphological expression of phospholipidosis.