Two new quinazoline-quinoline alkaloids, luotonins E (1) and F (2), were isolated from the aerial parts of Peganum nigellastrum along with two known alkaloids 3-quinolinecarboxamide (3) and pegamine (4). The structures of luotonins E and F were determined to be the formulae (1) and (2) respectively, by spectroscopic and synthetic methods. In our survey on the components of Peganum nigellastrum Bunge (Zygophyllaceae), Chinese medicinal plant "Luo-luo-zao", we have reported the structures of new alkaloid components luotonins A, B, C, and D isolated from the aerial parts of the plant. Furthermore, total synthesis of luotonin A, a cytotoxic pyrroloquinazolinoquinoline alkaloid against mouse leukemia P-388 cells, was achieved by three research groups, Ganesan's, Kelley's, and our groups. P. nigellastrum is a rich source of alkaloid compounds, and it has been reported that the basic fraction exhibited anti-tumor activity. Further extensive study on the alkaloid components of the plant has led to the isolation of two new alkaloids luotonins E (1) and F (2) along with two known alkaloids 3-quinolinecarboxamide (3) and pegamine (4). This paper deals with the isolation and the structure determination of the new alkaloids (1) and (2) by spectroscopic and synthetic methods.