Abstract The solubilities of 8 hydrocarbon gases in lipid bilayers have been determined at 25°C using a gas chromatographic technique. Results in 96% egg phosphatidylcholine, 4% phosphatidic acid bilayers expressed as Bunsen coefficients are: CH 4 0.20; C 2H 6 0.97; C 3H 8 3.6; n-C 4H 10 17; c-C 3H 4 11; i-C 4H 10 9.5; cis-butene 25; trans-butene 25. When 29 mol% cholesterol was incorporated with these phospholipids the Bunsen coefficient was reduced slightly. The observed solubilities are somewhat lower than those found in simple hydrocarbon solvents. The relative magnitudes of the solubilities of the gases in a given bilayer are closely related to the strength of their intermolecular forces. The solubility of butane was studied more extensively. No marked effects were observed when either surface charge or acyl chain saturation was increased, but the solubility in erythrocyte ghosts was much lower than that in lipid bilayers. The partition coefficient increased with decreasing temperature in egg lecithin and dimyristoylphosphatidylcholine. The entropy of solution in each case was more negative than that in isotropic non-polar solvents, and this accounts for the lower solubility in bilayers. The negative free energy of solution per CH 2 group for n-hydrocarbons is approximately twice that previously determined  for n-alcohols. This suggests that the concept of group contributions to solubility may not be universally applicable to lipid bilayers.