Two approaches have been used to develop nonmutagenic 5-nitroimidazoles. Both approaches are based on knowledge of the likely mechanisms by which this class of compounds cause mutagenicity. The first approach involved incorporating readily oxidizable gallate derivatives into the molecule. In one case, a very weakly mutagenic active antitrichomonal agent was obtained. The second approach involved incorporating a substituent at the C4 position of the ring. This generally resulted in a large reduction in mutagenicity and a lowering of antitrichomonal activity in vitro. In certain cases, however, mutagenicity was dramatically reduced while moderate antitrichomonal activity was retained. For example, 1,2-dimethyl-4-(2-hydroxyethyl)-5-nitroimidazole (5) showed good antitrichomonal activity in vitro (ED50 = 2 micrograms/kg) while possessing only 4% of the mutagenicity of metronidazole.