In this report the steady-state optical absorption and ligand rebinding kinetics of Fe(II)protoporphyrin IX (Fe(II)PPIX) and (CO)Fe(II)PPIX in tetramethylene sulfoxide (TMSO) are examined. The equilibrium optical absorption spectrum of Fe(II)PPIX in neat TMSO is characteristic of heme iron that is six-coordinate and low-spin suggesting the formation of a (TMSO) 2 Fe(II)PPIX complex. Absorption maxima are observed at 425 nm (Soret), 557 nm (a-band), and 529 nm (b-band). Addition of CO to a solution of (TMSO) 2 Fe(II)PPIX in neat TMSO results in a complex with absorption maxima at 415 nm (Soret), 566 nm (a-band), and 535 nm (b-band) consistent with the formation of a (CO)(TMSO)Fe(II)PPIX complex. The transient absorption difference spectrum subsequent to photolysis of the (TMSO) 2 Fe(II)PPIX complex displays an absorption maximum at 433 nm and a minimum at 423 nm that decays monophasically with a rate constant of (1.47 90.02)Γ10 6 s -1 consistent with the formation of a five-coordinate and high-spin transient. The corresponding transient absorption data obtained at 434 nm for the (CO)(TMSO)Fe(II)PPIX complex displays biphasic kinetics with a fast phase rate constant that is identical to the one obtained for photolysis of the (TMSO) 2 Fe(II)PPIX complex and a slower phase with a rate constant of (1.91 9 0.01)Γ 10 3 s -1 . The data suggest that the decay of this transient species involves rebinding of a TMSO to the heme iron followed by substitution of a bound TMSO with CO. Using these results the equilibrium constant for TMSO binding to the five coordinate (TMSO)Fe(II)PPIX complex is found to be 2.6 Γ10 3 M -1 . This value is roughly a factor of ten smaller than that of the DMSO complex. Molecular modeling studies suggest that geometrical distortions of the TMSO upon binding to the heme are responsible for the lower binding affinity.