Extracts of Hypoxis hemerocallidea corm (African potato) are commonly used by some traditional health practitioners in KwaZulu-Natal Province of South Africa as natural antenatal remedy to prevent threatening or premature abortion and miscarriage, and to ensure successful confinement. In this study, we investigated the uterolytic activity of H. hemerocallidea corm aqueous extract on spontaneous, rhythmic contractions of uterine horns taken from pregnant rats and guinea-pigs, as well as on spasmogen-provoked contractions of stilboesterol-primed, oestrogen-dominated, non-pregnant rat and guinea-pig isolated uterine horns. Relatively low to high concentrations of H. hemerocallidea corm aqueous extract (APE, 25-400 mg/ml) inhibited the amplitude of the spontaneous, rhythmic contractions of, and relaxed, uterine horns isolated from pregnant rats and guinea-pigs in a concentration-related manner. Furthermore, relatively low to high concentrations of APE (25-400 mg/ml) relaxed basal tones of uterine horns taken from non-pregnant, oestrogen-dominated rats and guinea-pigs in a concentration-dependent manner. The same moderately low to high concentrations of APE (25-400 mg/ml) inhibited acetylcholine-, oxytocin-, bradykinin-, and potassium chloride (K⁺)-induced contractions of oestrogen-dominated rat and guinea-pig isolated uterine horns in a concentration-related manner. Although the mechanism of uterolytic action of APE could not be established, the results of the present study lend pharmacological credence to the folkloric, ethnomedical uses of APE as a natural antenatal remedy for threatening or premature abortion, and suggest that the uterolytic action of the corm's extract is unlikely to be mediated via β₂-adrenoceptor stimulation, but probably mediated through a non-specific spasmolytic mechanism.