This review summarizes new findings on family 3 G-protein coupled receptors, also called metabotropic glutamate receptor (MGR) family, with respect to G-protein activation. In our studies we try to map the interface, which is crucial for G-protein activation. The interface includes intracellular loops of MGR, the loops 2 and 3 being especially important. On the GABAB receptor, the GB2 subunit contains enough molecular determinants for G-protein activation. Similarly to MGR, also here the corresponding intracellular loops are involved. On the G-protein side, the N-terminal preB1 region, C-terminal L9 loop and the extreme C-terminus are likely to contact the receptors in their active state.