Our previous work has indicated that normal development requires activities of prostaglandins in the embryonic tissue, and that a disruption of prostaglandin synthesis may lead to anomalies. We experimented to see if an antisense inhibition of the expression of cyclooxygenase 2 (Cox 2), which is rapidly inducible by many growth factors, may inhibit normal development of mouse embryos in culture. Swiss Webster mice embryos were prepared for culture on day 8, and an appropriate oligonucleotide was injected into the amniotic cavity. The antisense oligonucleotide was complimentary to the transcription initiation codon of the Cox 2 message and the next seventeen 3′ nucleotides. Complimentary sense oligonucleotide was used as a control. After a 24 hour culture, 85% of the embryos cultured without any injection developed normally. Antisense treatment reduced the percentage of normal embryos to 24%. The anomalies included open neural tubes, abnormal facial arches and craniofacial blebs. With the sense oligonucleotide, 70% of the embryos were normal. When antisense treated embryos were cultured in a medium containing 10ng/ml of prostaglandin E2, 67% of the embryos were normal. These results indicate that an inhibition of expression of Cox 2 produce anomalies in growing mouse embryos in culture, and that the anomalies may be caused by prostaglandin deficiency.