The cumulus oophorus surrounding eggs from C57BL/6 mice was digested by bovine or leech hyaluronidase significantly more rapidly than that surrounding eggs from BALB/c mice. The zona pellucida of C57BL/6 eggs was also more rapidly attacked by pronase. Three other sublines of C57BL showed the same characteristics. Measurements of susceptibility to hyaluronidase and pronase on eggs from the CXB recombinant inbred strains indicated that variation at a minimum of 2 loci affected each character. The lack of correlation between susceptibilities to the 2 enzymes across the recombinant strains implied that these differences separately affect the substrates of the enzymes, rather than reflecting a common difference in the process of oocyte maturation. The variation in susceptibility was unrelated to differences, controlled by the Ped and Qa-2 loci, in the rate of later embryonic cleavage. However, pronase susceptibility was significantly correlated with the early onset of the first cleavage.