Novel cytotoxic compounds, archazolid A and B, were isolated from the culture broth of strains of the myxobacteria Archangium gephyra and Cystobacter sp. Archazolids consist of a macrocyclic lactone ring with a thiazole side chain and showed high activity against mammalian cells. The IC50 values with different cell lines ranged from 0.1 to 1 ng/ml. An incubation of PtK2 potoroo cells with archazolid A (5 ng/ml) led to the formation of vacuoles in the ER, a phenomenon that is typical for inhibitors of V-ATPases, like concanamycin and bafilomycin. We therefore assume that archazolid is an inhibitor of the V-ATPase of higher cells.