First trimester exposure to isotretinoin is associated with an estimated 20% risk of major fetal malformations. Product labeling in force up to August 1988 included a statement that the drug is contraindicated in pregnancy and suggested procedures for prescribing physicians to follow to prevent inadvertent first trimester exposure to the product. This limited educational intervention did not prevent the continued occurrence of isotretinoin-related birth defects. The effectiveness of recent changes in the package labeling in preventing such birth defects remains to be demonstrated. Two infants with major birth defects associated with first trimester exposure to isotretinoin (Accutane, Roche Laboratories) were reported to the New Jersey Birth Defects Registry within 6 months. Stimulated by these reports, we sought additional cases in New Jersey and found three. We here describe these five cases of isotretinoin embryopathy, including available information on the circumstances which led to maternal use of isotretinoin during the first trimester of pregnancy. In response to a preliminary report of these cases and to investigations by epidemiologists at the U.S. Food and Drug Administration (FDA), the manufacturer altered the package labeling. The revised product information includes a more prominent "contraindication and warning" section and a new "patient information/consent" section. The effectiveness of this educational intervention should be evaluated.