The c-fos proto-oncogene mRNA is extremely labile and is rapidly degraded within minutes after being transported to the cytoplasm of growth factor-stimulated fibroblasts. Analysis of the structural determinants controlling c-fos message decay reveals that this message contains at least two functionally independent elements that are responsible for its short half-life. One of these determinants is an AU-rich sequence present in the 3' untranslated region of the c-fos message, whereas the other determinant, which is structurally unrelated to the AU-rich element, is located within the c-fos protein-coding sequence. Both the c-fos AU-rich element and the coding region instability determinant appear to function by facilitating rapid removal of the c-fos poly(A) tail as a first step in the mRNA degradation process.