Human theta (theta 1)-globin gene represents a member of the alpha-like globin gene family residing on chromosome 16. theta 1-Specific transcripts have been detected so far only in erythroid tissues and in erythroleukemia K562 cells. To investigate systematically its inducible expression and developmental specificity, we analyzed at the RNA level five additional human erythroleukemia cell lines with diverse developmental globin programs, two somatic cell hybrids between K562 and mouse erythroleukemia (MEL) cells, a human fetal liver x MEL somatic cell hybrid, and reticulocytes and bone marrow cells from normal adults. theta 1-Globin gene was expressed in all cell types. Inducible expression (two- to sixfold) was documented both in HEL and K562 erythroleukemia cells after 5-azacytidine treatment. Like K562 cells, HEL cells also displayed hemin-inducible theta 1-globin gene expression. Following transfer of human chromosome 16 from embryonic/fetal K562 to the adult MEL cells, theta 1-globin gene remained active but lost its potential for inducibility, suggesting probably a trans regulation mechanism. Higher levels of theta 1 mRNA were found in fetal liver cells compared with trace amounts in reticulocytes and normal adult bone marrow cells. These data clearly show that in contrast to the embryonic and adult patterns of expression of zeta and alpha-globin genes, respectively, theta 1-globin gene displays a different profile, being active predominantly during the early stages of ontogeny, switching to lower levels of expression in adulthood.