Previous studies have revealed a direct histaminergic projection from the tuberomamillary nucleus of hypothalamus to the cerebellum and a postsynaptic excitatory effect of histamine on the cerebellar interpositus nucleus neurons via histamine H(2) receptors in vitro, indicating that the histaminergic afferent inputs of cerebellar nuclei may be involved in the cerebellar function of motor control. To test this hypothesis, in this study histaminergic agents were bilaterally microinjected into the cerebellar interpositus nucleus of intact adult male rats, and their effects on motor balance and coordination of the animals performing accelerating rota-rod treadmill and balance beam tasks were observed. The results showed that microinjection of histamine into the cerebellar interpositus nucleus remarkably increased the time that animals balanced steadily on the rota-rod and markedly shortened the duration of passage through the balance beam, whereas GABA significantly depressed motor performances of animals on the rota-rod and beam, and normal saline influenced neither. In addition, administration of selective histamine H(2) receptor antagonist ranitidine considerably decreased the animals' endurance time on rota-rod and noticeably increased the passing time on beam, but selective histamine H(1) receptor antagonist triprolidine showed no effect. Furthermore, microinjection of histamine reversed the inhibitory effects of ranitidine on rota-rod and beam performance. These results demonstrate that histamine enhances rat motor balance and coordination through activation of histamine H(2) receptors in the cerebellar interpositus nucleus and suggest that the hypothalamocerebellar histaminergic projections may play a modulatory role on the cerebellar circuitry to ensure that movements are accurately executed.