A recombinant DNA marker has been identified to predict those individuals who will develop Huntington's Disease. It is important to determine when genotype positive individuals are developing the first manifestations of Huntington's disease. Furthermore, objective preclinical measures of disease would facilitate assessment of potential therapeutic interventions. We studied 4 patients with very early HD who were also tested with the Mini Mental State (MMS) and the Quantitated Neurological Examination (QNE) with I-123 IMP. SPECT acquisition began within 30 minutes and ROIs chosen from the transaxial SPECT slice corresponding to the CT cut containing the pineal and foramen of Monro. Compared to a group of 5 age-matched normal controls early HD patients showed significant decrements in caudate/cortex IMP accumulation. Values (mean ± SD) for HD patients were 75.3 ± 8.3 and for controls 86.9 ± 2.9 t=2.95, DF=7, p<0.05 (two tailed). Mini Mental State Score, Quantitated Neurological Examination, duration of disease and age showed correlations of +.51, -.99, -.98, -.97 and -.56. The first was influenced by the restricted range of the MMSS values. We conclude that: 1) IMP detected caudate to cortex differences in early HD patients, 2) all 4 persons had normal CT or MRI studies and 3) further studies are warranted to confirm and finalize SPECT's role in HD. Such studies are in progress.