The present study examined the effect of structural analogs of clonidine on feeding in both rabbits and monkeys. In rabbits, lofexidine and tizanidine either did not influence or decreased food intake in contrast to clonidine, which stimulated food intake. Lofexidine elicited easily observed decreases in motor behavior with several of the doses used in the study. Changes in motor behavior induced by tizanidine were more subtle. Conversely, lofexidine and tizanidine significantly increased feeding behavior in Stumptail macaque monkeys, as did clonidine. The results suggest that, in contrast to rabbits, Stumptail monkeys are more useful in searching for an 'orectic' effect of clonidine analogs.