Disruptions in mushroom body (MB) or central complex (CC) brain structures impair Drosophila associative olfactory learning. Perturbations in adenosine 3’,5’ monophosphate signaling also disrupt learning. To integrate these observations, expression of a constitutively activated stimulatory heterotrimeric guanosine triphosphate-binding protein alpha subunit (G alpha(s)(star)) was targeted to these brain structures. The ability to associate odors with electroshock was abolished when G alpha(s)(star) was targeted to MB, but not CC, structures, whereas sensorimotor responses to these stimuli remained normal, Expression of G alpha(s)(star) did not affect gross MB morphology, and wild-type G alpha(s) expression did not affect learning, Thus, olfactory learning depends on regulated G(s) signaling in Drosophila MBs.