Synthetic methods have been developed to allow for the preparation of two series of macrocyclic polyamide amphiphiles, with and without fluorescent nitrobenzoxadiazole (NBD) labels, using macrocyclic polyamine aza-crown ethers as starting materials. Each of the ten macrocyclic polyamides analyzed forms a stable monolayer at the air-water interface. The surface areas occupied by the macrocyclic polyamides at the air-water interface were determined using a Langmuir film balance and were found to be slightly larger than surface areas of computer molecular models based on the assumption that the amide and NBD-N groups are rigid and planar. Both monolayer and computer experiments have shown that there is a systematic trend of increasing surface area throughout the two series of macrocyclic polyamides.