Evidence suggests that the Ca2+/calmodulin-sensitive adenylyl cyclase may play a key role in neural plasticity and learning in Aplysia, Drosophila, and mammals. This dually-regulated enzyme has been proposed as a possible site of stimulus convergence during associative learning. This commentary discusses the evidence that is required to demonstrate that a protein in a second messenger cascade actually functions as a molecular site of associative integration. It also addresses the issue of how a dually-regulated protein could contribute to the temporal pairing (...) requirements of classical conditioning: that relationship between stimuli display both temporal contiguity and predictability. (shrink)