The ultrastructure of three human lymphoblastoid B cell lines, Raji, RPMI 4098, and WIL-2, was analyzed after the cells were incubated with tunicamycin, and antibiotic that selectively inhibits N-linked glycosylation of macromolecules. After a 24-hour exposure to 1.0 microgram/ml of tunicamycin, the lymphocytes lose their microvilli and become smooth spheres or develop a few blebs. Also, the cells show a dilation of the endoplasmic reticulum and an increase in myelin figures resulting from intracellular membrane accumulation, possibly lysosomal in origin. These ultrastructural alterations are similar to those observed in Tay-Sachs, Fabrey's, and Gaucher's diseases, Type II pneumocytes in viral pneumonitis, certain lysosomal storage diseases, and in aging fibroblasts. Therefore, tunicamycin-treated cells may be a useful model in the correlation of altered ultrastructural pattern in membrane flow with the etiology of certain diseases.