Abstract The human placental trophoblast component is of embryonic origin and is developmentally regulated; the tissue is highly proliferative and often described as pseudomalignant. Because cellular oncogenes have been implicated in normal cellular proliferation and differentiation processes, we have studied c myc oncogene expression in relation to the progression of human placental development. The c- myc transcript shows a 20- to 30-fold variation over the the course of placental development, with a peak at four to five weeks after conception. A clear decline in placental c- myc transcription is seen before the end of the first trimester of pregnancy. In situ hybridization to [ 125I]-labelled myc probes demonstrates an unequal distribution of myc transcripts in placenta, with particularly high expression in the cytotrophoblastic shell of the early placenta. The localization of myc transcripts to cytotrophoblast and the temporal pattern of myc expression support a strong correlation between myc transcript abundance and cytotrophoblastic proliferation. These findings are discussed in the light of a possible role for the c- myc gene in proliferation of normal cells.