Two new 3-alkylpyridine alkaloids, pyrinodemins E (1) and F (2), were isolated from an Okinawan marine sponge Amphimedon sp. and the structures of 1 and 2 were elucidated on the basis of spectroscopic data. Pyrinodemins E (1) and F (2) were novel 3-alkylpyridine alkaloids possessing a 4-(methoxyamino)piperidinone moiety and an indol-3-glyoxylamide moiety, respectively. Pyrinodemin E (1) showed cytotoxicity against P388 and L1210 murine leukemia cells.