Several polydactylous mutants affect the pattern of asymmetry along the anteroposterior axis of the vertebrate limb. In talpid2, diplopodia1, and diplopodia4 chick limb mutants, there is a preaxial extension that results in broader limb buds. Talpid2 shows reduction of the long bones and 9-10 syndactylous digits, none of which are specifically recognizable as members of the normal digit complement. In diplopodia1 and diplopodia4 extra digits are present preaxially in addition to the normal digits. This phenotype resembles the duplications obtained by grafting a polarizing region to the anterior margin of the limb bud. The abnormal skeletal pattern along the anteroposterior limb axis in both mutants suggests alterations in the signaling pathways that mediate growth and patterning of the limb. In situ hybridization studies reveal that whereas shh transcripts are restricted to the posterior limb margins, HoxD, Bmp-2, and Fgf-4 genes are ectopically expressed in the anterior region of the talpid2, diplopodia1, and diplopodia4 limb buds. The results obtained give insights into the molecular basis of talpid2 and diplopodia mutations and also into the possible roles of shh, Bmp-2, HoxD, and Fgf-4 genes in vertebrate limb morphogenesis.