The accumulation of carbonic anhydrase II (CAII) of chick embryonic red blood cells (RBCs) is triggered by hypoxic stress via hypoxic mediators (norepinephrine, adenosine). The process is accompanied by the induction of TIS7 and TOB which are known early response proteins of differentiating cell types. The anti-proliferative protein TOB has been characterized as a repressor of translation whereas TIS7 is discussed as regulator of muscle and neuronal differentiation. - The present investigation studied the induction, regulation, and localization of TOB and TIS7 in primitive and definitive RBCs to correlate the induction with the CAII synthesis: the TOB and TIS7 mRNA and protein are readily up-regulated in mid-stage definitive RBCs treated with cAMP-elevating agonists or within hypoxic chick embryos. Whereas TOB and TIS7 are synthesized in definitive RBCs until late developmental stages, more immature primitive and early definitive RBCs of early embryos induce the TIS7, TOB and CAII mRNA but fail to translate them into protein. In mid-stage definitive RBCs, TOB appears as short-lived cytosolic protein in advance to, while TIS7 is ribosome-bound and is present during CAII synthesis. In summary, we observe a differential response between early- and late-stage RBCs to cAMP due to regulation at the posttranscriptional level and which results in the synthesis of CAII and two translational regulators during hypoxic stress.