The solubility of an interleukin-2 (C125A) in an aqueous sodium dodecyl sulfate (SDS) solution was examined as a function of SDS concentration. A stock interleukin-2 solution at 1.1 or 0.31 mg/mL was mixed with one-tenth volume of a stock SDS solution at various concentrations. At intermediate SDS concentrations, the interleukin-2 showed nearly complete precipitation, while lower or higher SDS concentrations resulted in an increase in protein solubility. Circular dichroic analysis indicated that the protein remaining in the supernatant at low or high SDS concentrations has an altered conformation. Sedimentation velocity analysis of interleukin-2 in 0.1% SDS showed that about half the protein was monomeric, with the remainder as large aggregates with a broad size distribution from 20 to 100 S (M(r) approximately 10(5) - 10(7). In contrast, interleukin-2 in 0.01% SDS has a much smaller distribution of aggregates, sedimenting at ca. 2-10 S.