Intracytoplasmic globules have been described in a variety of neoplastic and nonneoplastic conditions, but remain poorly defined. In a review of 100 consecutive cases of lung carcinomas, six cases of mucin-positive adenocarcinoma demonstrated eosinophilic intracytoplasmic globules that ranged in size from less than 1 to 20 mu in diameter. The globules were often located adjacent to areas of tumor necrosis, and occurred either singly or multiply within individual tumor cells. Globules were similar in morphologic appearance to Russell bodies in plasma cells or the eosinophilic globules in hepatocytes of patients with alpha-1-antitrypsin deficiency, but were morphologically distinct from intracytoplasmic mucin vacuoles. The globules were brightly positive with PAS stain with diastase, were brick red with Masson's trichrome stain, and showed variably positive staining with Mallory's phosphotungstic acid-hematoxylin and Ziehl-Nielson stains. Immunoperoxidase staining showed slight staining of some globules with albumin, IgG, IgA, and alpha-1-antitrypsin. Ultrastructurally the globules had a homogeneous density and were often associated with profiles of rough endoplasmic reticulum. We suggest that these globules represent secretory glycoprotein accumulated in the cytoplasm of tumor cells in areas of tumor cell injury.