The frequencies of certain periodic behaviors of the nematode C. elegans are regulated in a dose-dependent manner by the activity of the gene egl-10. These behaviors are modulated oppositely by the activity of the G protein α subunit gene goa-1, suggesting that egl-10 may regulate a G protein signaling pathway in a dose-dependent fashion. egl-10 encodes a protein similar to Sst2p, a negative regulator of G protein signaling in yeast. EGL-10 protein is localized in neural processes, where it may function in neurotransmitter signaling. Two previously known and 13 newly identified mammalian genes have similarity to egl-10 and SST2, and we propose that members of this family regulate many G protein signaling pathways.