The clinical and biological heterogeneity of sickle cell hemoglobin (Hb) C disease (SC disease) is similar to sickle cell anemia, but has a much milder course. The effect of genetic factors such as alpha thalassemia or beta-globin gene haplotype has been analyzed in a limited number of cases. In this work, we report about 114 adult SC patients, aged 15 to 65 years (M/F = 0.93). The frequency of deletional alpha thalassemia (alpha(-3.7)) was found to be about 35%. The coinheritance of an alpha-thalassemia trait with SC disease had no effect on the hemoglobin level but hemolysis was significantly reduced. In these patients, as described for homozygous Hb S individuals, the Hb F level was higher in females than in males and in individuals carrying the beta(s)-Senegal haplotype. This haplotype involves the presence of an Xmnl site 5' to Ggamma, which is considered responsible for an increased Ggamma/Agamma ratio. Our survey showed that some genetic factors may modulate hematological parameters in SC disease.