The growth-regulating effects of pentagastrin, gastrin and the gastrin-receptor antagonist proglumide were investigated in three established cell lines derived from human colorectal carcinomas in vitro and after transplantation into nude mice. In vitro a significant increase of cell growth in the SW 403 cell line incubated with pentagastrin or gastrin was observed. In the Lovo cell line this effect was only detected after synchronization of cell growth. Pentagastrin and gastrin had no effect on the growth of the Ls 174 T cell line. Proglumide reduced cell proliferation in all three cell lines as well as in the L929S cell line derived from fibroblasts, which served as control. After transplantation into nude mice all tumor cell lines increased, Lovo and Ls 174 T as undifferentiated tumor, SW 403 as differentiated. Pentagastrin increased and proglumide decreased growth in SW 403 tumors, whereas no effect was observed on Ls 174 T and Lovo tumors. We therefore conclude that growth of some colorectal carcinomas is regulated by gastrin, but that the effect of proglumide is unspecific rather than related to blockage of gastrin receptors. The growth-regulating effect of gastrin could be due to tumor differentiation.