Many mammal species reproduce seasonally because of annual fluctuations in temperature, rainfall and photoperiod in often nutritionally challenging habitats. The reproductive biology of many small southern African mammals is largely unknown and in critical need of study. We investigated the breeding pattern of the female spiny mouse (Acomys spinosissimus) from South Africa. We examined the ovarian development, follicular growth, circulating plasma progesterone concentrations and the reproductive status of wild-caught adult female spiny mice sampled over a 12-month period while also correcting for body mass and age. From these data, we conclude that female A. spinosissimus breed seasonally. The main breeding season of the spiny mouse is between September and January, with plasma progesterone concentrations being elevated, ovarian volume and primary, secondary, tertiary and Graafian follicle numbers as well as the corpora body number being the highest and pregnancies occurring during this period. Females were reproductively inactive from February through to August. The breeding season coincides with the onset of the rainy season in the habitat, which starts around September and ends in April. Rainfall, in association with an increase in primary productivity and hence higher food availability, might be the most important factor shaping reproduction in the female spiny mouse.