This study was conducted to examine the neuropsychological effects of white matter and subcortical gray matter pathology. Nineteen patients with multiple sclerosis (MS), 16 with Huntington's disease (HD), and 17 normal controls (NC) participated. Participants completed the California Verbal Learning Test (CVLT), Rotary Pursuit (RP) and Mirror Tracing (MT) tasks, and the Symbol Digit Modalities Test (SDMT). The principal findings pertain to a dissociation in procedural memory: on RP, the HD group demonstrated impaired sequence learning compared to the MS group, which performed similarly to the NC group, yet on MT, the MS and HD groups demonstrated normal perceptual-motor integration learning. On the CVLT, both patient groups performed better on recognition than on recall. On the SDMT, both patient groups performed worse than the NC group, with the HD group performing more poorly than the MS and NC groups. These results suggest that involvement of white and subcortical gray matter may produce different neuropsychological effects.