Many cytokines (growth-factor proteins) are constructed from a common four-helix bundle structural framework. Rapid advances have been made in relating the structure and function of a growing number of four-helix bundle cytokines. This understanding opens the way to design de novo mimetics through such strategies as cytokine hybrids, structure-excerpted scaffolds and contact residue topology mimics. These may provide leads for agonists and antagonists of cell growth and differentiation.