H1(0) are H1 histone variants that accumulate in the chromatin of many differentiated tissues and may contribute to the modifications of transcriptional activities. Using B16 melanoma and Friend erythroleukemia cells, which can be induced to differentiate, I studied H1(0) mRNA translation regulation by measuring the H1(0) synthesis rate with radioactive labelling. It is first confirmed, in a new cellular model (B16 melanoma), that translation of H1(0) mRNAs is highly repressed during differentiation-induced accumulation of H1(0) protein. To show that this result was not merely reflecting an inefficiency in the translation of H1(0) mRNA, I used physiological and non-physiological methods to modulate H1(0) mRNA levels. Modifications of H1(0) mRNA levels appeared inefficient in changing the translation rate of H1(0) mRNAs. These results indicate that H1(0) mRNA levels may not always control the level of histone H1(0) synthesis which might be regulated independently from the mRNA level, probably in concert with the cellular stability of the protein.