The polymerization properties of the fully liganded fluoromet derivative of hemoglobin S (FmetHb S) were investigated by electron microscopy and absorption spectroscopy. Polymerization progress curves, as measured by increasing sample turbidity at 700 nm, exhibit a delay time (t(d)) consistent with the double nucleation mechanism. The pattern of fiber growth, as monitored by electron microscopy, is also indicative of a heterogeneous nucleation process, and dimensions of the fibers were found to be comparable to that of deoxyHb S. The polymerization rate constant (1/t(d)) depends exponentially on Hb S concentration, and the size of the homogeneous and heterogeneous nuclei also depend on FmetHb S concentration. As for deoxyHb S, higher concentrations of protein and phosphate favor fiber formation, while lower temperatures inhibit polymerization. Solubility experiments reveal, however, that eight times more FmetHb S is required for polymerization. The current studies further show that reaction order is independent of phosphate concentration if Hb S activity and not concentration is considered. The allosteric effector, inositol hexaphosphate (IHP), promotes fiber formation, and temperature-dependent reaggregation of FmetHb S suggests that IHP stabilizes pregelation aggregates. These studies show that FmetHb S resembles deoxyHb S in many of its polymerization properties; however, IHP-bound FmetHb S potentially provides a unique avenue for future studies of the early stages of Hb S polymerization and the effect of tertiary and quaternary protein structure on the polymerization process.