Two new sesquiterpene pyridine alkaloids, oppositines A (1) and B (2), have been isolated from the plant Pleurostylia opposita, collected in Sri Lanka. The compounds were isolated and purified by solvent/solvent partitioning, column chromatography, and HPLC. Their structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Oppositines A (1) and B (2) showed moderate cytotoxicity against HCT116 cell lines with EC50 values of 27 +/- 2 and 26 +/- 3 microM, respectively.