The relative proportions and tissue distribution of the long (Gsα-L) and short (Gsα-S) variants of the α subunit of the stimulatory G-protein (Gsα) change under a wide range of metabolic conditions, such as cellular differentiation, ontogenetic development, ageing and various adaptive processes. Although the two variants of Gsα are generally regarded to be functionally identical, this review summarizes recent experimental support for the non-identical behaviour of these proteins. Similarly, there is no consistent evidence for the functional meaning of these changes as far as regulation of adenylate cyclase activity is concerned. Since it is hard to believe that the complicated scheme of alternative splicing and the energy-consuming synthesis of proteins would be performed for no reason, it is suggested that Gsα variants might be involved in controlling other effector molecules and processes besides adenylate cyclase and cAMP metabolism. Such an idea is indirectly supported by specific alterations in the Gsα-L/Gsα-S ratio under various physiological and pathophysiological conditions.