The mixed interaction between human apolipoproteins C-I and A-II, each of which self-associate is aqueous solution, has been evaluated by sedimentation equilibrium measurements. In order to simplify data analysis apoC-I and apoA-II were modified by treatment with 2-nitrophenylsulfenyl chloride and tetranitromethane respectively. The molecular properties of the resulting derivatives, S-apoC-I and N-apo-A-II, each of which appreciable extinction coefficients above 350 nm, were indistinguishable from the corresponding unmodified species. Sedimentation equilibrium data were obtained with mixtures of S-apoC-I and native apoA-II, N-apoA-II and native apoC-I, and native apoC-I and native apoA-II. Mixed complex formation was detected readily with all mixtures investigated. The combined results were most consistent with a single mixed oligomer containing 2 molecules of apoA-II and 4 molecules of apoC-I. The corresponding equilibrium constant was 31248 +/- 890 (l/gm)5.