Summary.In order to ascertain the main target of the photodynamic effect with the sensitizer thiopyronine (TP) and its interference with cellular DNA, the uptake of TP into the yeast Saccharomyces cerevisiae and the distribution of the dye within the cells were studied. After fractionation of the cellular components, about 1% of the TP was found to be bound to the nucleus in anaerobically grown yeast cells; in aerobically grown cells, about 7% could be detected at the mitochondria.After careful isolation of the DNA from the organelles, only 0.024% of the dye once taken up by the cells was detectable at nuclear DNA, whereas 0.652% was bound to mitochondrial DNA. A calculation of the number of TP-molecules bound per nucleotides revealed a ration of one molecule TP per about 6,000 nucleotides of nuclear DNA and one molecule TP per 53 nucleotides of mitochondrial DNA. In vitro, the maximal binding capacity was estimated to be about one molecule TP per nucleotide.The induction of single strand breaks in the DNA after photodynamic treatment in vivo and in vitro was investigated by comparing the sedimentation of nDNA and mtDNA through alkaline sucrose-gradients. No differences in the sedimentation profiles of nDNA after photodynamic treatment of the cells in vivo as compared to the untreated control could be observed. In contrast, the sedimentation coefficient of mtDNA was significally decreased after photodynamic treatment, indicating the induction of single strand breaks in vivo only in mtDNA and not in nDNA.