Using a reverse transcription-polymerase chain reaction (RT-PCR) technique we determined the alpha 2/alpha 1, alpha/beta, and gamma/beta mRNA ratios in reticulocytes of 11 patients with seven different unstable beta chain variants, of 4 patients with two unstable alpha chain variants, in hemoglobin (Hb) D, Hb Porto Alegre, and Hb E heterozygotes, and in 8 patients with Hb X-beta 0-thalassemia (thal) (three D-beta 0-thal, one Porto Alegre = beta 0-thal, one Lulu Island-beta 0-thal, and three E-beta 0-thal). In addition, we determined the beta X/beta A mRNA ratios (X = unstable) in some Hb D heterozygotes and in 6 subjects with an unstable beta chain variant. Normal alpha/beta and beta X/beta A mRNA ratios were found in all heterozygotes tested, indicating that the respective mutations did not alter the stability of the mRNAs. The alpha/beta mRNA ratio in four Hb E heterozygotes averaged 4.21 (normal, 4.47), and that in 2 patients with Hb E-beta 0-thal and four alpha-globin genes (alpha alpha/alpha alpha) averaged a high 22.4. The gamma mRNA level in the Hb E heterozygotes was < 1% but varied greatly in patients with Hb E-beta 0-thal; the alpha/(gamma + beta) mRNA ratios in the 2 patients were 15.5 and 16.7, respectively. The large differences in alpha/beta and alpha/(gamma + beta) mRNA ratios in reticulocytes of subjects with AE and with E-beta 0-thal may be due to differences in the levels of normally-spliced beta E and abnormally-spliced beta E mRNAs. Only the latter is unstable and is preferentially produced in bone marrow and reticulocytes of Hb E-beta 0-thal patients, where it is rapidly degraded.