We have isolated and mapped an X-linked recessive mutation in Drosophila that blocks associative learning, and have partially characterized it biochemically. The mutation affects adenylate cyclase activity. Cyclase activity from mutant flies differed from the wild-type enzyme in that it was not stimulated by calcium or calmodulin. Mutant cyclase activity did respond to guanyl nucleotides, fluoride, and monoamines, which suggests that the defect is neither in the hormone receptor nor in either known GTP-binding regulatory protein. The mutation possibly affects the catalytic subunit directly. We postulate that there is at least one other type of adenylate cyclase activity that is unaffected by the mutation and insensitive to calcium/calmodulin.