FEMALE Drosophila melanogaster with environmentally(1-3) or genetically(4) elevated rates of mating die younger than controls. This cost of mating is not attributable to receipt of sperm(5). We demonstrate here that seminal fluid products from the main cells of the male accessory gland are responsible for the cost of mating in females, and that increasing exposure to these products increases female death rate. Main-cell products are also involved in elevating the rate of female egg-laying, in reducing female receptivity to further matings and in removing or destroying sperm of previous mates(6-12). The cost of mating to females may therefore represent a side-effect of evolutionary conflict between males(13).