Cell membranes from mouse L-cells (L-B82), rat hepatoma (HTC-H1) and 3 clones of their somatic cell hybrids (O7, V4a and V5) showing different degrees of density-dependent inhibition of growth were analyzed by polyacrylamide gel electrophoresis. The membrane polypeptides of the hybrid clones were all similar and all showed higher proportions of polypeptides with MW of 56,000 and 45,000 than their parents or their normal counterparts. The major glycoprotein from cell hybrids appeared to be identical with that of rat liver or rat hepatoma cells and different from that of L-cells. One hybrid showed density-dependent inhibiton of growth; the other 2, like both parents, did not. All produced tumors in nude mice, although tumor production by the hybrids was delayed. A large external protein (MW 240,000) iodinated by lactoperoxidase-catalyzed reaction was virtually missing in the parents but was present at high levels in all their hybrid clones. There was a lack of correlation between the presence of this protein, growth control in vitro and tumorigenicity. Furthermore, no correlation was seen between agglutination of these cells by Concanavalin A and tumorigenicity. The factors controlling these membrane properties thus are independent of density-dependent inhibition of growth and of those controlling the expression of cancer.