The reduction of hemoglobins (Hb) M such as Hb M Iwate, Hb M Boston, Hb M Hyde Park, Hb M Saskatoon, and Hb M Milwaukee by the ferredoxin and ferredoxin-NADP reductase system was studied systematically under anaerobic conditions. The enzyme system could not reduce the abnormal chains in methemoglobin M with an alpha chain anomaly but effectively converted the methemoglobin M with a beta chain anomaly to the fully reduced form. During the reduction of the methemoglobin M with a beta chain anomaly, the spectra showed a shift of the initial isosbestic points, indicating the possible formation of intermediate hemoglobins in the partially reduced state. On the reduction mode of the methemoglobin M, however, it was classified into three types. 1) Only normal chains were reduced (Hb M Iwate and Hb M Boston). 2) Sequential reduction from normal to abnormal chains occurred (Hb M Milwaukee and Hb M Hyde Park). 3) Normal chains were preferentially reduced, but the reduction of abnormal chains also started at the same rate when the reduction of normal ones had proceeded halfway (Hb M Saskatoon). These differences are discussed in relation to the redox potential of each abnormal chain in methemoglobin M.