TOP mRNAs are vertebrate transcripts which contain a 5′ terminal oligopyrimidine tract (5′ TOP), encode for ribosomal proteins and elongation factors 1α and 2, and are candidates for growth-dependent translational control mediated through their 5′ TOP. In the present study we show that elongation factor 2 (EF2) mRNA is translationally regulated in a growth-dependent manner in cells of hematopoietic origin, but not in any of three different non-hematopoietic cell lines studied. Human β1-tubulin mRNA is a new member of the family which contains all the hallmarks of a typical TOP mRNA, yet its translation is refractory to growth arrest of any of the examined cell lines. Transfection experiments indicate that the first 29 and 53 nucleotides of the mRNAs encoding EF2 and β1-tubulin, respectively, contain all the translational cis-regulatory elements sufficient for ubiquitously conferring growth-dependent translational control on a reporter mRNA. These results suggest that the distinct translational regulation of TOP mRNAs reflects downstream sequences which can override the regulatory features of the 5′ TOP in a cell type-specific manner. This notion is further supported by the fact that mutations within the region immediately downstream of the 5′ TOP of rpS16 mRNA confer onto the resulting transcripts growth-dependent translational control with a cell type specificity similar to that displayed by EF2 mRNA.