AbstractA technique was developed for the intrauterine application of teratogens to study fetal rat malformations produced by benzhydrylpiperazine compounds. Millipore filters (0.2 × 0.2 cm) impregnated with 50 μg chlorcyclizine HCl, 50 μg norchlorcyclizine HCl, or HCl alone were inserted through the uterine wall and placed on either the intact amniotic sac (over the fetus) or the placenta. Filters containing norchlorcyclizine implanted on the amniotic sac on day 13 or 14 produced 30% cleft palate, while chlorcyclizine filters produced only 3% cleft palate. Limb anomalies were also seen after norchlorcyclizine‐ or chlorcyclizine‐filter insertion. The optimal time of producing these malformations was day 13 or 14 of gestation. The agents exerted localized teratogenic activity since insertion of norchlorcyclizine filters over the head area of day‐14 fetuses resulted in 42% cleft palate, while those placed over the hindlimb produced only 11% cleft palate but 55% hindlimb malformations. Control HCl filters inserted over the fetus and norchlorcyclizine filters placed on the placenta produced no malfo