The gamma-subunit of the cGMP-phosphodiesterase (PDE gamma) of retinal rods forms a tight complex with the activated alpha-subunit of transducin (Gt alpha GTP gamma S). We observe that while PDE gamma is not the physiological effector of other G alpha subtypes, it can still detectably interact with them. This interaction is strong with Gi1 alpha and Gi3 alpha (Kd approximately 10 nM) and weaker with Go alpha and Gs alpha (Kd approximately 1 microM). For all these G alpha subtypes, similar intrinsic fluorescence changes are observed upon PDE gamma binding. Moreover, similar relative decreases in affinity are obtained when the GDP forms of Gi1 alpha, Gi3 alpha or Gt alpha are used in lieu of the GTP forms. This points to a conserved GTP-dependent effector-interaction domain.