The teratogenic action of thalidomide was investigated in rabbits, rats, hamsters, and mice. Peroral administration of 50, 150, and 300 mg/kg to New Zealand White rabbits, from 4 to 16 days of gestation, elicited dose dependent fetal anomalies. Besides arthrogryposis, the following other defects in tissues of mesenchymic origin were noted in order of decreasing frequency: pes varus, absence or marked shortness of tail, pes valgus, arachnodactyly, syndactyly, pendulous dolichodactyly, philtrum, and polydactyly. Mice of the CF₁ and ICR strain and inbred SJL, CBA, C₅₇ mice did not produce malformed fetuses after treatment with 200 mg/kg p.o. of thalidomide during pregnancy. A slight increase in resorption was also observed in placebo-treated mice (ICR). In rats (Long-Evans and Dunning-Fischer strains) and hamsters, 150 mg/kg of thalidomide from day 3 to 12 of pregnancy did not produce significant fetal changes. Arachnodactyly was noted in 8% of the Dunning-Fischer inbred rats. Fetal resorptions after thalidomide were not significantly altered in either species when compared with the respective control groups. In Long-Evans rats, rendered hypovitaminotic by diets deficient in riboflavine, pantothenic acid, or α-tocopherol, the embryotoxic effect was enhanced by the daily peroral administration of 150 mg/kg of thalidomide during pregnancy, as evidenced by the increased number of fetal resorptions or malformations.