Microcystins, isolated from toxic blue-green algae, are potent inhibitors of protein phosphatases 1 and 2A. Recently, we have reported that microcystin LR has a potent tumor-promoting activity on rat liver initiated with diethylnitrosamine. The structure of microcystins is unique in having an unusual amino acid, 3-amino-9-methoxy-10-phenyl-2,6,8-trimethyl-deca-4(E),6(E)-dienoic acid (Adda), which is thought to be significant for the activity. Geometrical isomers at C-7 in the Adda portion of microcystins, 6(Z)-Adda microcystins LR and RR, have been isolated from cyanobacteria. To estimate their tumor-promoting activities and to understand the importance of the Adda portion for activity, the maternal microcystins LR and RR and their isomers were subjected to examination of their interaction with protein phosphatases 1 and 2A and the release of glutamic pyruvic transaminase from rat liver. 6(Z)-Adda microcystins LR and RR bound to protein phosphatases 1 and 2A, inhibited their activities and released glutamic pyruvic transaminase from rat liver into serum, ten to one hundred times more weakly than the maternal microcystins LR and RR. These results indicated that the conjugated diene with 4(E),6(E) geometry in the Adda portion is important in the interaction with protein phosphatases.