Pdn/+ female mice, mated with Pdn/+ males, were treated with 40 mg/kg body weight of all-trans-retinoic acid (RA) intraperitoneally on day 10 or 11 of gestation, and effects on the limb development were investigated. RA treatment induced the shortening of stylopodium and zygopodium. In the present experiment, we focused on the differences between genotypes in the shortening of stylopodium and zygopodium induced by RA. The effects of RA were milder in Pdn/Pdn than +/- (Pdn/+ and/or +/+) fetuses. The differences between genotypes in the effects of RA were more significant in the group treated on day 11 than on day 10 of gestation. Cartilage of stylopodium and zygopodium was longer in day-13 Pdn/Pdn embryos exposed to RA on day 11 of gestation than those in similarly treated +/- embryos. Many apoptotic cells were observed in the mesenchyme of the forelimb plates at 12 hr after injection of RA on day 11 of gestation. These results suggest than the Pdn gene might influence the apoptosis induced by RA in the mesenchymal cells of the limb, causing milder effects in the shortening of stylopodium and zygopodium in Pdn/Pdn fetuses.