Bicontinuous cubic (Q(II)) phases composed of hydrated lipids are a unique mesoporous organic material. The diameter of the water channels in the range of 5-10 nm could be used as a reservoir for macromolecular therapeutic agents. Here, we describe the synthesis of water-soluble poly(amidoamine) (PAMAM) dendrimer derivatives labeled with fluorine and their diffusion in the water channels of a Q(II) phase. A Q(II) phase with Ia3d symmetry was prepared by hydration of a 9:1 molar mixture of polymerizable monoacylglycerol and the corresponding 1,2-diacylglycerol. The dendrimers having fluorine were synthesized by Michael reaction of PAMAM dendrimers with a mixture of ethyl 4,4,4-trifluorocrotonate and methyl acrylate. The hydrated diameter of the fluorinated dendrimer of generation 2.5 (G2.5AFH) is 32.6 A as measured by F-19 NMR. The diffusion coefficient of G2.5AFH at 25 degreesC in the water channels of the Q(II) phase, determined by pulsed field gradient F-19 NMR spectroscopy, is 1 X 10(-12) m(2)/s, which is compared to the free diffusion coefficient of the dendrimer in water (1.42 x 10(-10) m(2)/s). These data indicate that small globular proteins or similar molecules can diffuse rapidly enough in stabilized Q(II) phases to be technically useful.