Pregnant Lister Hooded rats were dosed orally with chlorocyclizine (60 mg/kg), promethazine (5 and 10 mg/kg) or doxylamine (500 and 750 mg/kg) (histamine H₁ antagonists prescribed for nausea of pregnancy) over the period of organogenesis (days 7–13). Fetuses were removed by caesarian section on day 21 and stained with Alizarin Res S and Alcian Blue for calcified bone and cartilage respectively. There were no significant differences in fetal size with any of the treatments; however, all 3 antagonists caused dose-dependent loss of skeletal integrity and marked fragility compared to the controls. By dosing dams on selected days, skeletal fragility was seen in all fetuses; the most marked effects occurring after dosing on days 10–12. Prolonging the gestation period with progesterone (10 mg/dam orally) resulted in normal sekeletal calcification but fetuses were still very fragile. Therefore, histamine H₁ antagonists may interfere with the development of rat fetal joints.