Abstract: The invention provides a method of killing replicating or non-replicating, transfected or transduced mammalian cells and bystander cells, comprising the following steps: (a) transfecting or transducing mammalian cells with a nucleic acid encoding a non-human purine nucleoside phosphorylase (PNP); and (b) contacting the transfected or transduced cells with an amount of a substrate for the purine nucleoside phosphorylase sufficient to produce a toxic purine base-analog thereby killing the transfected or transduced cells and bystander cells. In the present method of killing cells, the non-human purine nucleoside phosphorylase can be an E. coli purine nucleoside phosphorylase. The method of the invention described above can utilize a substrate that is a purine nucleoside analog. For instance, in the method provided in the Examples, the substrate is 9-(.beta.-D-2-deoxyerythropentofuranosyl)-6-methylpurine (MeP-dR).