Chloroquine is a critically important antimalarial drug and a well known intercalator into DNA. We now show that chloroquine binds more avidly to poly(dG-dC).poly(dG-dC) than to other synthetic polynucleotides and that this binding inhibits both salt- and cobalt-induced transitions to Z-DNA. These data are consistent with the possibility that chloroquine's toxicity to malarial parasites is mediated by its effect on DNA.