The W^sh is a mutant allele at the W (c-kit) locus of mice, but no significant abnormalities are found at the coding region of the W^sh allele. Since cultured mast cells derived from the spleen of W^sh/W^sh mice do not express messenger RNA (mRNA) of c-kit, we studied the interrelation between the number of mast cells and the magnitude of c-kit mRNA expression in the skin of W^sh/W^sh mice of various ages. The number of mast cells in the skin of W^sh/W^sh embryos of 18 days postcoitum (pc) was approximately 40% that of normal control (+/+) embryos, but the number of mast cells decreased exponentially after birth; the number dropped to 0.6% that of +/+ mice at day 150 after birth. A weak but apparent signal of c-kit mRNA was detectable in the skin of 18-day pc W^sh/W^sh embryos by RNase protection assay but not in the skin of 5-day-old W^sh/W^sh mice. The number of c-kit protein-containing cells was significantly greater in the skin of 18-day pc W^sh/W^sh embryos than in the skin of 5-day-old W^sh/W^sh mice. The abolishment of c-kit mRNA expression appeared to be specific, because the expression of mast cell carboxypeptidase A mRNA but not of c-kit mRNA was detectable by in situ hybridization in skin mast cells of 5-day-old W^sh/W^sh mice. Taken together, the expression of c-kit mRNA was abolished first, then the content of c-kit protein dropped to undetectable levels, and then the disappearance of W^sh/W^sh mast cells themselves followed.