The purpose of the study was to test the hypothesis that Huntington's disease (HD) is associated with impairment of procedural learning. We identified 13 patients with mild to moderate HD whose manual performance was still sufficiently intact to assess learning on the serial reaction time (SRT) task. Twelve age-matched neurologically normal control subjects were studied as well. The SRT task was a four-choice reaction time task in which the stimuli followed a sequence (10 items in length) which repeated itself 10 times during each of the first four blocks of trials. During the fifth block of trials, the stimuli were random. Learning was manifested by a reduction in response latency over the first four blocks and an increase in response latency in the fifth (random) block. Learning in this task has been demonstrated in other amnesics of other etiologies. The HD patients were significantly impaired on sequence-specific learning, using the log-transformed reaction time data (P less than 0.004). In addition, in an individual-by-individual analysis, five of the HD patients and none of the control subjects failed to show sequence-specific learning, a difference in proportions that was significant (P less than 0.04). No feature of the standard cognitive or motor assessment of the HD patients was associated with efficacy of procedural learning. HD, including patients with mild disease, was associated with a deficit in procedural learning, consistent with the hypothesis that the striatum plays a critical role in supporting procedural learning.