AbstractD‐Penicillamine (DPA) causes axial skeletal defects in rats and fetal lethality when given as 0.83% and 1.6% of the diet, but its mechanism of action on the axial skeleton is unknown. We have been using submerged fetal CD‐1 mouse limb‐bud organ cultures to evaluate the mechanisms of teratogenesis in the developing murine limb. Before attempting to evaluate thein vitroeffects of DPA, a dose response morphological teratology study was undertaken using CD‐1 mice to determine the effects of DPA on the mouse and determine the potential of using the mouse limb‐bud assay to investigate the terata produced by DPA. Groups (n= 8) of nulliparous pregnant mice (vaginal plug = day 0 of gestation) were dosed, via oral gavage, with 0, 250, 500, 1000 and 2000 mg kg−1DPA for the first 12 days of gestation. Body weights and food consumption were measured daily. On day 18, fetuses were removed by Caesarian section. Two‐thirds of the fetal skeletons were stained with alcian blue and alizarin red and then cleared and examined for defects. Soft‐tissue defects were examined in the remaining one‐third using a modification of the Wilson freehand technique. Maternal body weight gains were not different before day 12 of the experiment, but differed in the interval of day 13–18 (P= 0.004). No group differences were noted in male/female ratios, site of implantation, implantation numbers and number of fetuses. Decreased survivability was seen in the 2000 mg kg−1group. No treatment‐related defects were seen. As the main purpose of this experiment was to determine a dose at which limb defects occurred, the results indicate that the CD‐1 mouse does not appear to be a good model for DPA