A variety of genotoxic agents can induce an accumulation of p53 protein in the nuclei of mammalian cells and lead to either growth arrest or apoptosis in a p53-dependent manner. Recently, the induction of the p53 pathway has also been reported for non-genotoxic agents such as heat shock and hypoxia, rendering it likely that p53 activity might be triggered by a wider range of cellular stress factors. Here we report the effect of calcium phosphate-mediated transfection, a technique commonly used in studies of transient gene expression in mammalian cells, on fibroblasts containing wild-type p53. Incubation with a calcium phosphate precipitate results in a transient growth arrest in the presence or absence of plasmid DNA. The effect is accompanied by a rise in p53 protein levels and increased transcription of a p53-dependent reporter construct and is not observed in fibroblasts derived from p53 knockout mice.