Regulation of the transcription of the glycine decarboxylase gene and the H-protein gene was examined in chicken. Northern analysis suggested and run-off transcription confirmed that the glycine decarboxylase gene transcription is exclusively tissue-specific and takes place at different efficiencies in liver, kidney, and brain which are the chicken tissues exhibiting the glycine cleavage activity. No evidence for the glycine decarboxylase gene transcription was obtained in heart, spleen, and skeletal muscle. Basal and tissue-specific transcription of the H-protein gene can be distinguished. The tissue-specific transcription coordinates with transcription of the glycine decarboxylase gene in active tissues, while low abundance H-protein and its mRNA, products of the basal transcription, exist in inactive tissues together with small amounts of T-protein. Apparently, T-protein is synthesized by a process similar to that for H-protein. Glycine decarboxylase mRNA levels show a linear relationship with H-protein mRNA levels and with specific activities of the glycine cleavage reaction in active tissues. Tissue-specific distribution of the glycine cleavage activity is primarily determined by the expression of the glycine decarboxylase gene. The coordinate and tissue-specific transcription of the genes for the constituent proteins plays a key role in determining the magnitude of the glycine cleavage activity in chicken tissues and, thereby, the tissue-specificity of glycine metabolism.