With the growing awareness that the G protein beta and gamma subunits directly regulate the activities of various enzymes and ion channels, the importance of identifying and characterizing these subunits is underscored. In this paper, we report the isolation of cDNA clones encoding eight different human gamma subunits, including three novel forms designated gamma 4, gamma 10, and gamma 11. The predicted protein sequence of gamma 4 shares the most identity (60-77%) with gamma 2, gamma 3, and gamma 7 and the least identity (38%) with gamma 1. The gamma 4 is modified by a geranylgeranyl group and is capable of interacting with both beta 1 and beta 2 but not with beta 3. The predicted protein sequence of gamma 10 shows only modest to low identity (35-53%) with the other known gamma subunits, with most of the differences concentrated in the N-terminal region, suggesting gamma 10 may interact with a unique subclass of alpha. The gamma 10 is modified by a geranylgeranyl group and is capable of interacting with beta 1 and beta 2 but not with beta 3. Finally, the predicted protein sequence of gamma 11 shows the most identity to gamma 1 (76% identity) and the least identity to the other known gamma (33-44%). Unlike most of the other known gamma subunits, gamma 11 is modified by a farnesyl group and is not capable of interacting with beta 2. The close resemblance of gamma 11 to gamma 1 raises intriguing questions regarding its function since the mRNA for gamma 11 is abundantly expressed in all tissues tested except for brain, whereas the mRNA for gamma 1 is expressed only in the retina where the protein functions in phototransduction.