Longicin [1] and (2,4-cis and trans)-goniothalamicinone [2], two new monotetrahydrofuran Annonaceous acetogenins, have been isolated from the leaves and twigs of Asimina longifolia (the long leaf paw paw) by the use of the brine shrimp lethality test for bioactivity-directed fractionation. The structures were elucidated based on spectroscopic and chemical methods. Compound 1 was converted to its ketolactone isomer, (2,4-cis and trans)-longicinone [3], to aid the stereochemical elucidation of 1. Compounds 1-3 showed selective and potent cytotoxicities to certain human tumor cell lines, with the potency of 1 against pancreatic carcinoma (PaCa-2) over one million times that of adriamycin. Nine known cytotoxic acetogenins, annonacin, xylomaticin, isoannonacin, gigantetrocins A and B, muricatetrocins A and B, gigantetrocin-A-one and goniothalamicin, were also isolated for the first time from this species.