There is burgeoning interest in the dissolution of inhaled medicines in the lungs and speculation that a biopharmaceutics classification system (BCS) concept, analogous to that currently used for oral drug dosage forms, may be extended to pulmonary drug products. This exposes the need for reliable and relevant methods for measuring the solubility in the lungs, especially for poorly soluble drugs for which dissolution is thought to be an important determinant of their pharmacokinetics and pharmacodynamics in the lungs. Inhaled corticosteroids (ICS) are a widely used class of anti-inflammatory agents for the treatment of respiratory disease which includes drugs with low aqueous solubility, i.e. fluticasone propionate (FP) and beclomethasone dipropionate (BDP). The solubility of such drugs has been reported in a variety of simulated lung lining fluids of different compositions. The purpose of this study was to compare drug solubility in solvents typically used to represent lung lining fluid. The solvents investigated in this study were based on a physiological salt solution (Gamble’s solution), a licensed lung surfactant product (Survanta®) and a synthetic simulated lung lining fluid (sLLF) based on the measured composition of human lung lining fluid. Drug solubility was compared in five solutions in total: ultrapure water, Gamble’s solution, sLLF, an aqueous dilution of Survanta, and Survanta itself. The solubility of FP in these solvents was 1.92, 1.99, 2.04, 3.89 and 20.28 μg/mL, respectively. BDP solubility in the same solvents was 2.17, 1.03, 16.79, 5.78, to 37.16 μg/mL, respectively. These data illustrate that simulated lung fluids that contain surfactant have enhanced potential to dissolve inhaled steroid drug particles that have deposited in the lungs.