Tubuloreticular structures were induced in human umbilical vein endothelial cells cultured in media containing recombinant interferon alfa and beta but not in media containing recombinant interferon gamma or other agents that induce interferon, such as 5-bromodeoxyuridine or polyinosinicpolycytidylic acid. Recombinant interferon beta induced tubuloreticular structures in endothelial cells at a lower concentration and in a greater percentage of cell sections than recombinant interferon alfa. This report of tubuloreticular structures being induced in vitro in nonlymphoid cells provides evidence that interferon is the substance that causes the formation of tubuloreticular structures in endothelial cells in vivo.