The solution structure of the Pd-II-bleomycin A2 complex was resolved by NMR spectroscopy in combination with molecular modelling. The preparation of the complex in 1.0 M NaCl aqueous solutions leads to the formation of a major compound, which is very stable at ambient temperature. Our NMR spectroscopic data demonstrate that bleomycin is coordinated through the beta-aminoalanine secondary amine, the pyrimidine ring N1, the deprotonated histidyl amide and the imidazole N1, in contrast to an earlier study that proposed coordination of the valerate amide. 2D NMR spectroscopic data were used as distance constraints in simulated annealing molecular-dynamics calculations and the first solution structure of a square-planar metallo-bleomycin is reported. In order to assess the toxicity of Pd-II-bleomycin, cytotoxicity measurements were performed in U937 and K562 leukemia cell lines using two methods. In both cell lines the free drug and the complex exhibit similar toxicity as a function of time. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).