A 37-year-old man of Guyanese origin was found to have homozygous beta-thalassemia without anemia. There were no physical stigmata of thalassemia. The hematocrit value was 41 to 45.8, the mean corpuscular volume was 61 fL, and the mean corpuscular hemoglobin was 18.9 pg. The HbF was 45% with a G gamma:A gamma ratio of 3:1. An acid elution preparation of the peripheral blood showed heterogeneous distribution of HbF, but all erythrocytes stained for fetal hemoglobin. The beta/alpha synthesis ratio in the peripheral blood was 0.25; the (beta + gamma)/alpha ratio was 0.55. Haplotype analysis revealed homozygosity for the -+-+ + + + pattern (Senegal, type IX) at seven polymorphic restriction sites within the beta-like gene complex. Digestion of DNA with Xmnl indicated that the -158 C-to-T transition was present in both beta-globin gene clusters. Oligomer hybridization analysis demonstrated homozygosity for the -29 A-to-G mutation in the beta-globin promoter region. Although this form of thalassemia can cause transfusion-requiring anemia, the high-HbF, high-G gamma phenotype associated with the linked +-+ + subhaplotype and -158 C-to-T substitution appears to have ameliorated the disease in this subject.