The dunce gene of Drosophila melanogaster codes for a cyclic adenosine-3',5'-monophosphate-specific phosphodiesterase. Mutations of dunce alter or abolish the activity of this enzyme, produce elevated cAMP levels, cause recessive female sterility, and produce learning deficiencies in both sexes. Aberrant male sexual behavior has also been associated with the memory defects of dunce mutants. Here we show that the longevity of dunce mutant females, homozygous for null-enzyme alleles, is reduced by 50% in the presence of males compared to control dunce females kept without males. Mutant dunce females, mate every 22-24 hr. We propose a cause-effect relationship between mating and reduced longevity. Pheromones or peptides transferred during mating may activate adenylate cyclase and create an increase in cAMP levels that cannot be damped in dunce females. This increase may affect basic physiological functions and lead to reduced longevity.