Paired pulse transcranial magnetic stimulation (TMS) gives an indication of the balance between intracortical inhibitory and excitatory circuits. In normal subjects, at interstimulus intervals (ISIs) between 1-6 ms the test motor potential (MEP) evoked in the hand muscles is inhibited by a conditioning subthreshold shock, while at longer ISIs (10-25 ms) it is slightly facilitated. We investigated the cortico-cortical interactions in the opponens pollicis muscle of 11 Huntington's disease (HD) patients (7 males, 4 females; aged 19-62 years). TMS was performed with two Magstim 200 stimulators connected to the same stimulating round coil, positioned flat over the vertex, through a Bistim module. Stimulus intensities of 80 and 125% of motor threshold at rest were used for the conditioning and test shock. No difference of MEP threshold and amplitude was observed between HD patients and controls. The test MEP was less inhibited (MANOVA: P < 0.0001) at short ISIs and more facilitated (P < 0.05) at long ISIs in symptomatic HD patients, while ipsilateral cortico-cortical interactions were normal in two asymptomatic HD patients. The average value of inhibition, at ISIs 2-5, was correlated inversely (r - 0.71) to the onset-age of HD and directly to the dyskinesias rating (r 0.67), but not to the UHDRS motor score. Abnormalities of motor cortical excitability can be demonstrated in HD by paired pulse TMS.