In many hybrid cell systems fusion of normal cells to tumorigenic cells suppresses the transformed phenotype. We have now examined the expression of anchorage independence, one characteristic of the transformed phenotype, in hybrids between different anchorage-independent Chinese hamster fibroblasts. Examination of many different crosses was facilitated by a rapid screening procedure. Instead of isolating individual hybrid clones, the fraction of hybrid cells that were anchorage independent was estimated directly after fusion and compared to the total hybrid recovery. Seven different anchorage-independent cell lines were crossed to derivatives of the previously characterized CHEF/16 tumorigenic cell line. Two of these cell lines gave anchorage-independent hybrids, while the 5 others gave anchorage-dependent hybrids. These results support previous observations with interspecies hybrids that the transformed phenotype can be suppressed in hybrids between transformed cells. We interpret these results as showing that there are at least two alternative genomic changes by which Chinese hamster fibroblasts can become anchorage independent.