Journal of Pest Science, 2018; 91 (1): 157–168Rodent pest management traditionally relies on some form of lethal control. Developing effective fertility control for pest rodent species could be a major breakthrough particularly in the context of managing rodent population outbreaks. This laboratory-based study is the first to report on the effects of using fertility compounds on an outbreaking rodent pest species found throughout sub-Saharan Africa. Mastomys natalensis were fed bait containing the synthetic steroid hormones quinestrol and levonorgestrel, both singly and in combination, at three concentrations (10, 50, 100 ppm) for 7 days. Consumption of the bait and animal body mass was mostly the same between treatments when analysed by sex, day and treatment. However, a repeated measures ANOVA indicated that quinestrol and quinestrol + levonorgestrel treatments reduced consumption by up to 45%, particularly at the higher concentrations of 50 and 100 ppm. Although there was no clear concentration effect on animal body mass, quinestrol and quinestrol + levonorgestrel lowered body mass by up to 20% compared to the untreated and levonorgestrel treatments. Quinestrol and quinestrol + levonorgestrel reduced the weight of male rat testes, epididymis and seminal vesicles by 60–80%, and sperm concentration and motility were reduced by more than 95%. No weight changes were observed to uterine and ovarian tissue; however, high uterine oedema was observed among all female rats consuming treated bait at 8 and 40 days from trial start. Trials with mate pairing showed there were significant differences in the pregnancy rate with all treatments when compared to the untreated control group of rodents.