The formation of aggregates, rather than correctly folded polypeptide chains is a pressing problem in biotechnology that has been difficult to approach quantitatively. The competition between folding and aggregation has been carefully analyzed for bovine growth hormone (bGH) and can be attributed to incorrect helix-helix docking for this foul helix bundle protein. An extended molecular thermodynamic model reported here represents Gibbs energy changes associated with intramolecular and intermolecular helix-helix dockings occurring during protein folding and protein aggregation. The model incorporates (1) a semiempirical local composition Gibbs energy expression to account for the helix-helix hydrophobic interactions, which favor helix-helix docking and aggregation and (2) a Flory-Huggins-type Gibbs energy expression to describe the configurational entropy of the polypeptide backbone conformation, which favors disaggregation. For the folding and aggregation of bGH, the molecular thermodynamic model provides estimates for the Gibbs energies and thermodynamic stabilities of various conformations of bGH and qualitatively accounts for the competition between aggregation and productive folding. It also successfully describes the inhibition of aggregation found with peptides corresponding to bGH helical sequences and the effect of site-directed mutagenesis.