Normal septation and alignment of the outflow tract of the heart depends on ectomesenchymal cells derived from the cardiac neural crest. Removal of the premigratory cardiac neural crest results in a variety of cardiac anomalies. The sequence of events leading to these cardiac anomalies in the absence of the cardiac neural crest cell population is not fully understood. This study is the first in a series directed at understanding the role of the neural crest in cardiovascular development at the molecular level. We have begun by distinguishing proteins uniquely expressed by, or responding to the presence of, cardiac neural crest cells in the pharyngeal apparatus, as well as proteins that are seen in the absence of cardiac neural crest cells. Cardiac neural crest was removed by microcautery from stage 9 to 10 embryos. At stages 14, 18, and 21, the protein patterns in the pharyngeal regions of experimental and sham-operated embryos were compared using isoelectric focusing followed by SDS-polyacrylamide gel electrophoresis. Five proteins were found in sham-operated embryos at stages 14 and 18 that could not be seen in embryos with neural crest ablations. Four proteins were found in embryos with neural crest ablation at stages 14 and 18 that were not seen in sham-operated embryos. By stage 21, the protein patterns of both sham-operated and experimental embryos were identical. These results indicate that there may be a compensatory response to neural crest ablation as development proceeds.