High-resolution two-dimensional polyacrylamide gel electrophoresis was performed on the pancreatic cell lines SG, SG-R, FG, and L3.5, which when injected into the spleen of nude mice produced hepatic metastases in 0%, 20%, 64%, and 100% of the animals, respectively. A total of 981 proteins were quantitatively identified. In the highly metastatic lines, 13 proteins were present in statistically significant greater quantities, while 4 proteins were present in statistically significant greater quantities in the cell lines with a low metastatic potential. Two proteins were unique to the highly metastatic lines, while 16 proteins were unique to the lines with a low metastatic potential. These results suggest that there are considerable quantitative and qualitative differences in the cellular proteins of human pancreatic cancer cell lines with a varying metastatic potential and imply a biochemical basis to tumor heterogeneity and metastases.