This work reports the chemical composition and cytotoxic evaluation of the essential oils from three different samples of the leaves of Porcelia macrocarpa R. E. Fries (Annonaceae). The crude oils, obtained by hydrodistillation procedures, were chemically analyzed by GC/MS. The obtained data indicated the predominance of sesquiterpenes (89.8 +/- 0.7%), the main compounds being germacrene D (47 +/-+/- 1%) and bicyclogermacrene (37 +/- 1%). These oils also contained the monoterpene verbanyl acetate (0.5 +/- 0.06%) and the diterpene phytol (1.2 +/- 0.3%). The crude oils obtained from leaves were pooled and tested in vitro against six cancer cell lineages--murine melanoma (B16F10-Nex2), human glioblastome (U87), human cervical carcinoma (HeLa), human leukemia (HL-60), human colon carcinoma (HCT), human breast adenocarcinoma (SKBr), and human melanoma (A2058), as well as against a non-tumorigenic human cell line (HFF). Since the essential oil reduced more than 50% of the viability of several tumor cells at 100 microg/mL, indicating the presence of active compounds, the crude material was subjected to fractionation over a SiO2/AgNO3 column. This procedure afforded different fractions composed of pure as well as different mixtures of bicyclogermacrene and germacrene D, which were tested against the same tumor cell lines, indicating a significant cytotoxic potential against HL-60 cells. These results suggested that the crudeoils and their components, mainly germacrene D, could be used as prototypes for the development of new anti-cancer agents for the treatment of human leukemia.