The Hb F levels in beta-thalassaemia can be affected by factors both linked and unlinked to the beta-globin gene cluster. We have recently analysed a group of patients with a homozygosity for the IVS-I-6 (T-->C) mutation, showing a wide variation in Hb F levels (2-47%) which could not be accounted for by any sequence variation within regulatory elements of the beta-globin gene cluster. In order to further investigate factors underlying this phenotypic difference we have developed a competitive reverse transcription/polymerase chain reaction procedure and used this method to determine the relative amounts of gamma- and beta-mRNAs in 10 patients with the IVS-I-6 homozygosity and 15 heterozygous parents, two IVS-I-6/delta beta-thalassaemia compound heterozygotes, five homozygotes for the beta(+) IVS-I-110 (G-->A) mutation, and in two with a homozygosity for the beta(0) codon 39 (C-->T) mutation. Three heterozygotes were also included. The percentages of gamma/(gamma(+) beta) mRNA were 10-73% in the IVS-I-6 homozygotes and < 2% to 10% in their heterozygous parents. A direct relationship existed between the level of mRNA and the % Hb F. However, the relative gamma-mRNA levels in the IVS-I-6 homozygotes were higher than their Hb F levels, indicating a possible competition between the gamma and beta transcripts for translational factors with a less efficient initiation of protein synthesis on the gamma-mRNA or a preferential survival of cells with mainly beta-globin gene expression at the post-reticulocyte stage. The gamma-mRNA levels in the two IVS-I-6/delta beta-thalassaemia compound heterozygotes were 71% and 62%, similar to their Hb F levels (63% and 59%), and averaged 82% (range 65-91%) in the five IVS-I-110 homozygotes, and 97.5% in the two codon 39 homozygotes. The correlation between these values and the % Hb F could not be evaluated because of the transfusion regimens; however, the levels of gamma-mRNA were as expected for patients with these beta-thalassaemia alleles.