Dot blot hybridization was used to determine the relative amounts of the beta-major and beta-minor globin RNAs present in reticulocytes of mice at 14.5 and 17.5 days of gestation, newborns, and adults of the Hbab/Hbab;Hbbs2/Hbbs2 globin genotype. RNAs isolated from embryonic yolk sac, fetal liver, and adult reticulocytes were hybridized with the following labeled DNA probes: alpha-1, beta-minor specific, and beta-major specific. The level of beta-sminor RNA in reticulocytes at 14.5 and 17.5 days of gestation is nearly the same as in induced reticulocytes of adult mice. In contrast, the level of beta-s2major RNA in reticulocytes at 14.5 days of gestation is 0.23 X and at 17.5 days of gestation is 0.66 X the amount found in reticulocytes of adult mice. These results correlate well with earlier observations that the beta-sminor globin gene approaches its normal adult level of expression by 14.5 days of gestation, whereas the beta-s2major globin gene expression increases between 14.5 days of gestation and 6 days postnatally. They indicate that the differential expression of beta-sminor and beta-s2major globins during development is regulated at the level of transcription. Expression of the beta-minor globin gene in reticulocytes of adult normal mice is not maximal, however, because the levels of the beta-minor globin and its RNA are increased further in reticulocytes of thalassemic mice.