Female CD-1 mice were mated with CD-1 × T/ + F1 males that were heterozygous for the brachyury (T) semidominant lethal gene or were +/+. Fetuses from CD-1 × +/ + matings were normal when observed on gestation Day 17 (plug day = Day 0). Those from the CD-1 × T/+ cross exhibited the expected 1:1 ratio of short:normal tail lengths, but 10% of these fetuses were tailless, apparently due to factors in the CD-1 genotype that increased the expressivity of the T-gene with regard to reduction of tail length. Additional CD-1 females were mated with CD-1 × tw18/+ F1 males. Fetuses from the CD-1 × tw18/+ matings were normal. CD-1 females carrying CD-1 X +/+, CD-1 × T/+, or CD-1 × tw18/ + litters were injected ip on gestation Day 9 with 30 mg/kg cycloheximide or were untreated. Cycloheximide was teratogenic for litters from all three crosses. Polydactyly, oligodactyly, and a variety of skeletal abnormalities were observed. Gross malformations and total skeletal malformations were increased in treated CD-1 × T/ + or tw18/ + litters in comparison with CD-1 × +-/ + litters, as were nonvertebral skeletal defects in CD-1 × tw18/+ litters. Prenatal mortality was also greater in treated mutant-containing litters than in + / + litters, and fetal weights were similarly decreased in treated CD-1 × tw18/ + litters. The incidence of taillessness was also higher in treated (26%) than in control (10%) CD-1 × T / + litters. Thus both the T and tw18 alleles appear to have enhanced the teratogenicity of cycloheximide, and the inhibitor may have increased the expressivity of T.