The effect of three environmentally important metals, arsenic, selenium, and chromium, on the accuracy of DNA synthesis in vitro has been analyzed. The addition of arsenic to fidelity assays did not significantly alter accuracy. Selenium did not alter fidelity under normal conditions of magnesium activation, nor did it affect the mutagenicity of manganese. Chromium in the form of Cr(III) as well as Cr(VI) diminished the fidelity by which Escherichia coli DNA polymerase I copies polynucleotide templates. Nearest-neighbor analysis of the product synthesized in the presence of chromium indicates that the misincorporated in the presence of chromium indicates that the misincorporated bases are present as single-base substitutions. Chromium was also mutagenic using the recently developed phi chi 174 assay, which measures the fidelity of DNA synthesis with a natural DNA template.