A series of formamidines structurally related to clonidine were synthesized and investigated as potential nonopiate analgesics. Several of these compounds showed potent analgesic activity (ED50 on HCl writhing less than 1.0 mg/kg) with low potential for hypotensive effects. A qualitative description of the structure-activity relationship of this series reveals that the 2,4- and 2,6-dimethylphenyl compounds are more potent analgesics than are the corresponding dichlorophenyl compounds.