TheDrosophilamemory mutantrutabaga(rut) has been previously shown to have a defective subpopu-lation (or functional state) of the enzyme adenylate cyclase. We report here that the reduced adenylate cyclase activity is also associated with a defective responsiveness of the enzyme to forskolin. Forskolin activation isotherms of the enzyme in normal membranes reveal low- and high-affinity forskolin-interacting components; the residual enzyme in the mutant shows a smaller proportion of the high-affinity response. In addition, in mutant membrane preparations, forskolin fails to shift theKmof the enzyme for free Mg2+and for MgATP, in contrast to the situation in the normal tissue. The defect in the responsiveness to forskolin inrutis even more pronounced in a Lubrol-solubilized enzyme preparation, and is due to intrinsic properties of the cyclase system rather than to the absence (or presence) of a soluble, or detergent solubilized, factor inrut. The reduced forskolin responsiveness maps to the X chromosomal segment 12F5-6 to 13A1-5, within the region previously reported to span the locus that controls both the abortive memory and the lack of Ca2+-stimulation of adenylate cyclase inrut17. The possible relevance of the findings to postulated molecular mechanisms of short-term memory formation is discussed.