Fetal hemoglobin (Hb F) is the most studied modifier of sickle cell disease. Coinheritance of high Hb F determinants such as δβ-thalassemia (δβ-thal) and hereditary persistence of fetal hemoglobin (HPFH) can contribute to raised Hb F concentration in these patients. One hundred and seventy-six cases of sickle cell disease with high Hb F were screened for the presence of the Asian Indian deletion-inversion (G)γ((A)γδβ)⁰-thal and HPFH-3 (Indian, 48.5 kb) disorders. Three cases from two unrelated families were found to have sickle cell disease and the ((A)γδβ)⁰-thal genotype. Three other members had heterozygous (G)γ((A)γδβ)⁰-thal. None had HPFH-3. Despite very high Hb F concentrations and linkage of the β(S) gene to Asian haplotypes, the compound heterozygotes had severe clinical presentation, possibly because of heterocellular distribution of Hb F. In conclusion, these high Hb F determinants are not common causes of high Hb F in Indian sickle cell disease patients.