The water-soluble metal content of 1950s London smogs and modern particulate matter (PM) are associated with adverse health effects. This study aimed to elucidate the bioreactivity of these metals alone and in mixtures and to investigate the comparative bioreactivities of a surrogate mixture and a PM sample. These revealed similar bioreactivities. A bioreactivity hierarchy of these metals was established: Fe2+ > Cu2+ > Fe3+ > VO2+ > Zn2+ > As3+ = Pb2+ = Mn2+ = VO3-. Secondary components (i.e., chlorides, sulfates, nitrates) did not affect metal bioreactivity, whereas oxidation state was important. Synergism was observed between zinc and various metal ions (Cu2+, Fe3+, VO2+). In conclusion, low-valence transition metals are key to PM bioreactivity.