Abstract Cyclic AMP (CAMP) is known to be an important mediator of gene expression in eukaryotic cells. At present, little is known about the developmental events which render specific genes responsive to cAMP in distinct cell types, or about the biochemical mechanisms by which cAMP exerts these regulatory effects. By examining the effects of cAMP treatment on specific mRNA levels in Dictyostelium discoideum cells with different ‘developmental histories’, we defined the developmental states in which specific genes display responsiveness to CAMP. We focused on two specific rapid responses: the ability of cAMP to inhibit the expression of an ‘early’ developmentally regulated mRNA (discoidin-I) and to stimulate the expression of a ‘late’, prespore-specific mRNA (PL3). Using this approach, we showed that, for both mRNAs, the ability to respond rapidly to cAMP is absent from vegetative cells grown on bacteria, and is acquired during development on filters. Furthermore, we identified several developmental states in which the discoidin-I response to cAMP is present. but in which the PL3 response is not. In experiments designed to examine the effects of cAMP analogues on the levels of these two mRNAs, we demonstrated that the analogue specificities of the discoidin-I and PL3 responses are different, and that the specificity for the PL3 response depends on the developmental state. The developmental kinetics and analogue specificity of the PL3 response suggest a two-step mode of action of cAMP in activating the expression of this gene. We discuss possible implications of these findings for the mechanisms of action of exogenous cAMP as well as for the role of cAMP in controlling the changes in gene expression that accompany normal development.