Different growth-and cell surface properties of cells grown from skin biopsy samples from 25 Huntington's chorea patients, 22 at risk patients, and agematched controls were examined in a blind study. The number of explants obtained from each biopsy was carefully controlled. The nature (epithelial or fibroblastic) of the initial outgrowth was scored on all explants and the mean number of cells obtained from each explant after 3 weeks in culture was determined after trypsinization. During the next 15 passages, various parameters characterizing cell growth were studied. Maximal cell densities and growth rates were examined using a standard plating density of cells at each passage. These growth properties were also examined in three media: DME-NCS, DME-FCS, and Ham's F10 fetal calf serum (FCS). In addition, the effects of high temperature (40°C) and the addition of insulin to the medium on the growth and protein content of the cells was examined. These results, containing 152 measurements on 81 cases, were examined using a phased multivariate analysis. Blind cluster analysis showed that the clusters were nonrandomly determined. Factor analysis indicated the initial growth parameters to be among the most discriminating. Discriminant analysis, however, did not prove to be of any diagnostic use, since the external factors masked any possible genetic difference. Two possible sources of bias were identified: the size of the biopsy and the type of culture medium. The cell surface properties of HD and control fibroblasts were further investigated using two different techniques. The adhesion of single HD cells to either HD cell layers or normal cell layers revealed no significant differences. Intradermal immunization of rabbits with whole fibroblasts resulted, with both cell lines, in a polyspecific antiserum containing antibodies directed against a number of surface components. When HD and control fibroblasts were compared with the two antisera, no qualitative or quantitative differences in the precipitation patterns obtained using crossed immunoelectrophoresis, (CIE) were found. Our investigations did not allow us to discriminate HD cultures from controls by any of the qualitative and quantitative parameters tested.