The application of supercritical carbon dioxide to particle design has recently emerged as a promising way to produce powders of macromolecules such as proteins and genes. Recently, an insulin powder for inhalation was approved by authorities in Europe and the USA. Other macromolecules for inhalation therapy will follow. In the 1990s proteins were precipitated with supercritical CO(2) from solutions in an organic solvent such as dimethylsulfoxide, which caused significant unfolding of protein. Since 2000, aqueous solutions of proteins and genes have generally been used with a cosolvent such as ethanol to precipitate in CO(2). Operating conditions such as temperature, pressure, flow rates, and concentration of ingredients affect the particle size and integrity of proteins or genes. By optimizing these conditions, the precipitation of proteins and genes with supercritical CO(2) is a promising way to produce protein and gene particles for inhalation.