Recombinant Interleukin-2 (IL-2) is expressed in E. coli as insoluble aggregates; a protocol has been developed for solubilization, renaturation and purification of IL-2 from such aggregates at the 5-10-mg level. IL-2 aggregates were isolated from soluble proteins by centrifugation, subjected to a 1 M guanidine hydrochloride wash and a butan-1-ol wash (the latter to remove lipid), dissolved in 8 M guanidine hydrochloride-10 mM dithiothreitol and partly purified by gel permeation chromatography. Refolding/oxidation was then performed by dilution into Tris-HCl, pH 8.5 containing 1.5 microM copper sulphate to accelerate autoxidation. Final purification was by successive cation-exchange and reversed-phase high-performance liquid chromatographic steps, yielding over 99.5% pure IL-2 with an overall recovery of 20%.