The general pharmacological properties of guanabenz (Wy-8678), a new centrally acting antihypertensive agent, on the central nervous system were studied in mice, rats and rabbits, and they were compared with those of clonidine. In mice, guanabenz (1-30 mg/kg, i.p.) showed overt sedation dose-dependently, like clonidine (0.3 or 1 mg/kg, i.p.). At doses (2.5-20 mg/kg, p.o.) not causing muscle relaxant action, guanabenz impaired rotarod performance, inhibited conditioned avoidance responses and maximum electroshock seizure, prolonged thiopental sleeping time, and lowered body temperature in rats. These central depressant effects were observed following oral administration of clonidine at much lower dose levels. In rabbits, neither guanabenz (5-20 mg/kg, p.o.) nor clonidine (0.5 or 1 mg/kg, p.o.) affected body temperature. These findings suggest that the central depressant activities of guanabenz, qualitatively very similar to clonidine, are much less potent than those of clonidine.