We have measured the membrane/water partition of free fatty acids, of a fluorescent analogue, and of chlorpromazine into plasma membranes from lymphoma, platelets, red cells, and liposomes of egg phosphatidylcholine. Three different methods were used: hygroscopic desorption [ Conrad , M.J., & Singer, S.J. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 5202-5206; Conrad , M.J., & Singer, S.J. (1981) Biochemistry 20, 808-818], centrifugation, and fluorescence titration. The partition coefficients for chlorpromazine and all fatty acid/membrane combinations were in the range 10(2)-10(5). No significant partition difference was observed between liposomes and plasma membranes. These results suggest, therefore, that fatty acids and chlorpromazine can readily partition into artificial and cell plasma membranes.