A protein known as heat-shock factor-1 (HSF1) is a major transactivator of stress-inducible genes in response to environmental changes, but it is also implicated in extra-embryonic development and female fertility in mice^,. Here we show that mouse embryos whose mothers lack this protein are unable to develop properly beyond the zygotic stage, although oocytes were ovulated and fertilized normally. Wild-type spermatozoa do not save zygotes from lethality, indicating that the reproductive failure of females deficient in this factor is caused by a 'maternal effect' mutation, and that HSF1 from the mother normally controls early post-fertilization development.