Enzymes and transporters that catalyse reactions involving inorganic carbon are well characterized with respect to the species of inorganic carbon (CO2 or HCO3-) with which they interact. There is less information on the species recognized by proteins that sense inorganic carbon. In this issue of the Biochemical Journal, Hammer and colleagues show conclusively that cyanobacterial adenylyl cyclases are activated by CO2 and not HCO3-, as was believed previously. While in some circumstances a similar in vivo regulatory outcome is achieved from sensing HCO3- as from sensing CO2, there are cases in which the outcomes are significantly different. The most striking example is where a compartment lacks carbonic anhydrase yet supports large metabolic fluxes of inorganic carbon species so that CO2 and HCO3- are not at equilibrium. Other examples involve changes in pH, or temperature, of a compartment containing an equilibrium mixture of CO2 and HCO3-.