Cyclopia and related malformations have been observed as a lethal condition of fowl. The more important facts and conclusions may be summarized as follows: 1. The morphological expression varied from a condition in which the upper beak was rudimentary to microcephaly. The whole gamut of defects is referred to as perocephaly. This is subdivided into two groups, viz. ‘rudimentary upper beak’, comprising the low-grade defects, and ‘cyclopia’, under which heading we include malformations ranging from synophthalmia to microcephaly. In the rudimentary upper-beak condition the premaxillary bones are lacking. On rare occasions such chicks hatched; they were always blind. Synophthalmia and cyclopia are associated with a proboscis above the median orbit. In more extreme conditions only a median pigment spot was present, there was no oral opening and the ears were closer to the ventral midline than normally (otocephaly). The most extreme cases were microcephalic without any indications of eyes, mouth or ears. 2. Perocephalic malformations made their first appearance inF 2 and later generations . of crosses between recessive rumpless fowl and representatives of the following three breeds: Silver Gray Dorking, Rhode Island Bed and Jungle fowl. In sibships which included any embryos with these malformations, the incidence was about 2–3%. When families with a different breeding history were intercrossed, the incidence of perocephaly rose to about 5 %, and upon combining the genotypes of all sources of origin the frequency became about 13%. The proportions of rudimentary upper beak and cyclopic embryos remained nearly constant during these changes in total incidence of perocephaly. After the 13% level of incidence had been reached, all but the smallest sibships contained perocephalic embryos. Significant heterogeneity of incidence continued, however, to exist between the individual sibships of pen matings. 3. Twenty-one sons of perocephaly-producing parents were tested in our experiments. All transmitted the malformations. 4. A rising incidence of perocephaly was associated with increased early embryo mortality. 5. The sex ratio appeared to be normal among perocephalic embryos of all grades. 6. A scrutiny of the data obtained during four years showed in three of them a highly significant seasonal trend, the incidence of perocephaly rising from early toward late spring. The causes of this trend remain uncertain. 7. The results of our breeding tests led to the following interpretation. The genetic factors responsible for the occurrence of perocephaly (possibly a single recessive gene substitution) were present in the stock of recessive rumpless fowl. Except for extremely rare ‘ sporadic’ occurrences, the mutation was completely suppressed by modifying genes. The mutation came to light after outcrosses to unrelated stocks and the incidence rose with continued dilution of protective modifiers. It is evident that even in later generations many embryos which were homozygous for perocephaly developed normally. 8. It is suggested that, in fowl at least, the accumulation of recessive modifying genes with individually small effects, but which in concert can completely suppress the action of deleterious mutants, represents a common and important mechanism of equilibration and genetic self-defence.