Objective: To investigate and compare the direct effects of compounds used in the treatment of hypertensive disease in pregnancy on human umbilical artery resistance in vitro.Methods: Isometric tension recordings were performed under physiological conditions on human umbilical arterial rings (n=30). The in vitro effects of labetolol, hydralazine, alphamethyldopa, nifedepine and magnesium sulphate (at concentration ranges from 1 nanomolar to 1 millimolar), and their respective vehicle controls, were measured. Results were expressed as logEC (pD) and mean maximal inhibition values for each compound.Results: All compounds investigated, except alpha methyldopa, exerted a significant relaxant effect on umbilical arterial tone. Alphamethyldopa was significantly less potent when compared to all other compounds (mean maximal inhibition value [20.89 +/- 7.99%] versus all other agents [range 63.15 +/- 8.70-84.12 +/- 3.84%] (P<0.01)). The dose response curve of nifedipine yielded a significantly greater pD value when compared to that of hydralazine, labetalol, and magnesium sulphate (pD value [5.82 +/- 0.34] versus the above groups [range 3.10 +/- 0.09-3.52 +/- 0.14] (P<0.01)).Conclusion: These findings demonstrate that agents commonly used for the treatment of hypertensive disease in pregnancy, excluding alphamethyldopa, have significant direct effects on the fetoplacental circulation. These results suggest that alphamethyldopa administration during pregnancy is less likely to produce significant direct effects on fetal vasculature then other agents used.