The interaction of partially fluorinated carboxylic acids with a biologically relevant surfactant, dipalmitoylphosphatidylcholine (DPPC), was investigated at the air-water interface. The compression isotherms of mixtures of three partially fluorinated carboxylic acids (1-3) and their hydrocarbon analogues (4-6) with DPPC were recorded at various compositions on hydrochloric acid (pH = 1.9, 32 +/- 2 degreesC) as a subphase. The mixing behavior was assessed by analyzing the concentration dependence of the average molecular area at constant film pressure (area/mole fraction or A-X diagram). All six carboxylic acids (1-6) show a negative deviation from ideal behavior at surface pressures between 3 and 25 mN/m, which is indicative of an attractive interaction with DPPC in the mixed monolayer at the air-water interface. With the exception of nonafluorpentadecanoic acid (1), all carboxylic acids investigated show a concentration dependence of the breakpoint of the phase transition from the liquid-expanded to the liquid-condensed state, which supports the interpretation of the A-X diagrams.