Treatment of suspension cultures of human lymphoid cells with the halogenated pyrimidine 5-bromo-2′-deoxyuridine (BUDR) induced the formation of 20-28 nm diameter tubules within the endoplasmic reticulum. Up to 14% of cell sections examined by electron microscopy were involved. This effect was dependent upon the concentration of BUDR in the culture medium and the duration of treatment. The tubular structures "appeared within 72 hours after suspension of the lymphoid cells in 20 µg/ml BUDR. The morphological response to BUDR was completely blocked by simultaneous treatment of the cultures with excess thymidine (20 × 10-5M). The cell lines tested originated from patients with infectious mononucleosis (PGLC) and Burkitt's lymphoma (Raji). These lines were known to be infected by Epstein-Barr virus, but herpestype nucleocapsids or virions were never identified in the cells treated with BUDR. Ultrastructurally, the BUDR-induced tubules could not be distinguished from previously described “tubuloreticular structures” which appear clinically in the lymphocytes or vascular endothelial cells of patients with virus infection, systemic autoimmune diseases, or cancer, and which also occur spontaneously in some lymphocyte cultures from symptom-free individuals. Although the identity of tubuloreticular structures in patients and in vitro remains to be established by other than morphologic criteria, BUDR treatment of lymphoid cell cultures demonstrates that such structures can form selectively in response to a specific stimulus and provides an experimental model for further investigations.