G protein-coupled receptors (GPCRs) interact directly with heterotrimeric G proteins to transduce physiological signals. Early studies of this interaction concluded that GPCRs (R) and G proteins (G) collide with each other randomly after receptor activation and that R-G complexes are transient. More recent studies have suggested that inactive R and G are preassembled (precoupled) as stable R-G complexes. Here we examine the stability of complexes formed between cyan fluorescent protein-labeled alpha(2A)-adrenoreceptors (C-alpha2ARs) and G proteins in cells using fluorescence recovery after photobleaching (FRAP). Labeled G proteins diffused in the plasma membrane with equal mobility in the absence and presence of immobile C-alpha2ARs. Immobile C-alpha2ARs activated labeled G proteins, demonstrating functional coupling without stable physical association. In contrast, a stable R-G interaction was detected when G proteins were deprived of nucleotides and C-alpha2ARs were active, as predicted by the ternary complex model. Overexpression of regulator of G protein signaling 4 (RGS4) accelerated the onset of effector activation but did not detectably alter the interaction between C-alpha2ARs and G proteins. We conclude that at most a small fraction of C-alpha2ARs and G proteins exist as R-G complexes at any moment.