It has been demonstrated that the degree of agonist-induced desensitization of the beta(2)-adrenoceptor is related to agonist efficacy (strength of signalling), whereby high-efficacy agonists (e.g. formoterol) cause more phosphorylation and internalization of the receptor than low-efficacy agonists (e.g. salmeterol). These early studies, however, used a protocol where agonists were matched for receptor occupancy rather than functional effect. In this issue of the BJP, Duringer and colleagues have extended these studies to compare the ability of agonists to cause desensitization at equi-effective (cAMP signalling) concentrations rather than equal occupancy. Their data and conclusions are quite different from those previously described. After prolonged exposure, all the agonists caused a similar degree of desensitization, whereas a pulse protocol uncovered a greater loss of responsiveness with the low-efficacy ligands. This is consistent with the notion that high-efficacy agonists have 'spare receptors', and are therefore less sensitive to loss of receptors through desensitization. It also reflects experience in the clinic, where both formoterol and salmeterol show a similar early decline in bronchoprotection, after which their effects remain stable. These findings challenge the notion that high-efficacy ligands always cause more functional desensitization.