The S8 inhibitions of AKs from six different sources were studied in mammals, birds, fish, and a microorganism. All AKs tested were inhibited by S8. Except for carp, all inhibited AKs from those tested were reactivated by DTT. Inhibitions of AKs by other hydrophobic inhibitors, NEM, butanol and ethanol were also studied. The inhibitions by S8 suggest that the hydrophobic pockets in the AKs cover a wide phylogenetic range. All inhibitions by S8 are reactivated by DTT. Unlike the inhibitions by S8, the characteristics of inhibitions by the other hydrophobic inhibitors differed among the AK sources tested and none was the irreversible type. The data suggest that no covalent bonds were formed with NEM. Similarly, the ability to reactivate the inhibitions by DTT differed among the AK sources. The possibility that the hydrophobic domains in the AKs may serve as part of an enzyme activity control mechanism is discussed.