Roberts-SC phocomelia syndrome (RS) is a recessively inherited developmental disorder characterized by profound pre- and postnatal growth reduction, symmetrical limb reductions of varying severity, and craniofacial abnormalities. Many patients with RS exhibit a striking chromosomal abnormality involving the heterochromatic, C-banding regions of most chromosomes. Dermal fibroblast strains from three such patients were used to investigate in vitro cellular growth characteristics. Plating efficiency, colony-forming ability, and cell density at confluence in RS were compared with dermal fibroblast strains from pediatric patients without RS and fetal lung fibroblast strains. Time-lapse cinematography was used to study mitotic duration and cytokinesis in RS and various control fibroblast strains. Clearly, cell from affected individuals had deficiencies that led to a multitude of abnormalities at the cellular level. These included: abnormal mitosis and cytokinesis, reduced cell growth, atypical cell morphology, and altered chromosomal morphology at peri- and paracentromeric and nucleolar-organizing regions. These findings suggest that the basis for at least some of the phenotypic abnormalities characteristic of this trait may reside in the reduced growth rates of the cells during the course of development. This could account for the reduced pre- and postnatal growth rates as well as for the developmental abnormalities, since deficiencies of cells in developing anlagen could well lead to alterations in developmental patterns.