Piperine (CAS 94-62-2) is a constituent of various spices which are used as common food additives all over the world. The reproductive toxicity of piperine was studied in Swiss albino mice. Relevant short-term tests were employed to assess the effect on estrous cycle, mating behaviour, toxicity to male germ cells, fertilization, implantation and growth of pups. Piperine (10 and 20 mg/kg b.w.) increased the period of the diestrous phase which seemed to result in decreased mating performance and fertility. Post-partum litter growth was not affected by the piperine treatment. Sperm shape abnormalities were not induced by piperine at doses up to 75 mg/kg b.w. Considerable anti-implantation activity was recorded after five days post-mating oral treatment with piperine. The sex ratio and post-implantation loss were unaffected after treatment with piperine. Intrauterine injection of piperine caused the total absence of implants in either of the uterine horns (16.66%) or one of the horns (33%) of treated females. No histopathological changes were detected in the ovary and the uterus at the cellular level. Prostaglandin E1-induced acute inflammation of rat paw was significantly reduced after piperine treatment. Our results show that piperine interferes with several crucial reproductive events in a mammalian model.