The reduction of Phascolopsis gouldii methemerythrin Fe(III),Fe(III) to deoxyhemerythrin (Fe(II),Fe(II) consists of three stages, when monitored by UV-visible absorption. The first stage is dependent upon the concentration and nature of the reductant while the second and third stages are not. Rate constants, k(,2) and k(,3), for the latter stages have values of (TURN)2 x 10('-3)s('-1) and (TURN)2 x 10('-4)s('-1), respectively. The reduction of Themiste zostericola methemerythrin gives similar results. The time courses of UV-visible, EPR and Mossbauer spectra are used to support a new mechanism for the reduction of hemerythrin, which accounts for differences observed between hemerythrins isolated from the two species of sipunculid worms;The rates of reduction of Fe(III),Fe(III) (mu)-S('2-)methemerythrin (E(DEGREES)' = (TURN)298 mV) and methemerythrin (E(DEGREES)' = 110 mV versus NHE) to the Fe(II)Fe(III) semi-met level by two heme proteins and several inorganic reagents have been measured. Rates of oxidations of the corresponding semi-met forms have also been measured. When using an apparent physiological reducing agent, cytochrome b(,5) from Phascolopsis gouldii, the respective second order rate constants for reduction of (mu)-S('2-)methemerythrin and methemerythrin are 8900 M('-1)s('-1) and 160 M('-1)s('-1) at pH 7.5, 0.15 M Na(,2)SO(,4) and 25(DEGREES)C. When using the nonphysiological reducing agent deoxymyoglobin, the respective second order rate constants for reduction of (mu)-S('2-)methemerythrin and methemerythrin are 38 M('-1)s('-1) and 1.22 M('-1)s('-1) at pH 6.3, 0.15 M Na(,2)SO(,4) and 25(DEGREES)C. In all cases (excepting oxidation by Co(phen)(,3)('3+)) the relative rates for hemerythrin versus (mu)-S('2-)hemerythrin are shown to obey the Marcus relation. The rates of oxidation of cytochrome b(,5) by either (mu)-S('2-)met- or methemerythrin are 150-400 times faster than those of deoxymyoglobin. Factors contributing to the higher rates with cytochrome b(,5) are discussed;The carcinogen, chromate, slowly oxidizes deoxyhemerythrin to the semi-met level, k(,obs) = 3 ((+OR-)1) x 10('-5)s('-1), at pH 6.0, and stabilizes the conformation labelled (semi-met)(,O) for up to (TURN)60 hours. The value of k(,obs) is independent of chromate and protein concentrations and a reaction mechanism is proposed.