Resorcinol-dodecanal cyclotetramer forms stable monolayers at the air-water interface. Molecular interaction between this monolayer and substrates bearing hydrogen-bonding groups is studied. Sugars and water-soluble polymers bind to the monolayer selectively, resulting in its expansion. Selectivity of the sugar binding is different from that of extraction into CCl4: ribose gives significant effects in both systems, while fucose, which is readily extracted in CCl4, is less effective in the monolayer system. Xylose and galactose, which are complexed weakly in CCl4, provide strong effects on the πA isotherms. Binding of riboflavin is also examined by monitoring the absorption of the deposited monolayer and by deposition on the piezocrystal and frequency measurement. Complexation of the monolayer is made efficient owing to the dense packing of the hosts.