Mice homozygous for the E2 mutation were born at the expected frequency. Genotype analysis of pups derived from +/- by +/- matings revealed that +/+, +/-, and -/- mice were present at nearly the expected 1:2:1 frequency. Of the initial 60 animals genotyped, 19 (32%) were +/+, 27 (45%) were +/-, and 14 (23%) were -/-. Thus, the E2 gene was dispensable for normal embryonic development. However, as expected, nearly all homozygous mice died in the perinatal period. Immediately following birth, homozygous pups were indistinguishable from their +/+ and +/- littermates; they were vigorous, active and able to suckle. By mid to late day on postnatal day one, most -/- pups became moribund and were readily identifiable as they were lethargic, pale, and exhibited gasping respiratory movements. With few exceptions, -/- pups died within 72 hours of birth. We have observed one rare -/- pup that survived to postnatal day 13. The reason for the prolonged survival of this pup is unknown.