The signal transduction pathway controlling determination of the ident
ity of the R7 photoreceptor in the Drosophila eye is shown to harbor h
igh levels of naturally occurring generic variation. The number of ect
opic R7 cells induced by the dosage-sensitive Sev(S11.1) transgene tha
t encodes a mildly activated form of the Sevenless tyrosine kinase rec
eptor is highly sensitive to the wild-type genetic background. Phenoty
pes range from complete suppression to massive overproduction of photo
receptors that exceeds reported effects of known single gene modifiers
, and are to some extent sex-dependent. Signaling from the dominant ca
in-of-function Drosophila Epidermal Growth Factor Receptor (DER-Ellips
e) mutations is also sensitive to the genetic backgrounds, but there i
s no correlation with the effects on Sev(S11.1) This implies that diff
erent genes and/or alleles modify the two activated receptor genotypes
. The evolutionary significance of the existence of high levels of gen
etic variation in the absence of normal phenotypic variation is discus
sed.