This study was designed to determine the degree of resistance to hypotonic saline for different variants of blood hemoglobin that are found locally, relative to normal adult red cell hemoglobin and to one another. Blood specimens from 25 individuals, five for each type of hemoglobin variant, were exposed to varying degrees of hypotonicity at room temperature and the optical density (OD) was read after incubation. The pattern of hemolysis was consistent in all samples for each hemoglobin variant. HbAA was found to be most susceptible to saline hypotonicity, followed by HbAC and HbAS while HbSC and HbSS were highly resistant to lysis when exposed to varying degrees of hypotonicity. The three variants containing HbA, that is HbAA, HbAC, HbAS had close similarity in the pattern of hemolysis. Similarly, HbSC and HbSS exhibited a close pattern as well. We suggest that the pattern observed in the two categories may be as a result of the presence of the adult hemoglobin gene (A) in the former group and the presence of the sickle hemoglobin gene (S) in the latter, respectively. We observed that the pattern of susceptibility to saline hypotonicity found in these variants has an inverse relationship to the severity of clinical manifestation commonly observed in individuals having these different hemoglobin variants. Keywords: hemoglobin, morbidity, genotype, osmotic fragility, electrophoresis.