THE SPECIFIC response of individual tissues to a single steroid receptor cannot be explained simply by DNA sequence alone. For example, in the same animal a given steroid receptor is capable of interacting with the nucleus of two different cell types, resulting in unique gene expressions despite the presence of a similar genome. Historically, these differences in response to a single type of steroid receptor within target tissues in the same animal have been suggested to occur through different alterations in chromatin structure. However, the molecular mechanisms of this tissue specificity remain unexplained. It is possible that in different cell types the specific three-dimensional organization of the genome and cell skeletal elements interplay may vary to accomplish the hormonal regulation of specific gene expression. It is the purpose of this review to address the potential role of cell structure as a central component of hormone action.