For determination of the intracellular site of synthesis and the pathways followed by amyloid protein AA, immunocytochemical localization of the anti-AA reactive substance was investigated in the livers of CBA/J mice in an acute-phase response evoked by a single subcutaneous injection of 0.5 ml of 10% casein. In the cytoplasm of the hepatocytes, the positive reaction was localized on and/or in the rough endoplasmic reticulum and the single membrane-bound vesicles, vacuoles and lamellae including the Golgi apparatus, confirming that amyloid protein AA follows the common routes of synthesis and secretion established for other proteins. The anti-AA-reactive substance was also localized on the free surface of the hepatocyte membrane, including the microvilli. The latter reaction appeared as early as but lasted at least several hours longer than its cytoplasmic counterpart, suggesting that a certain retention period exists before the release of the AA-reactive substance from the cellular surface to the free blood plasma.