Villi from first trimester human placenta were exposed to oxygen concentrations of either 2%, or 20% during 3 hours to construct two reciprocally subtracted libraries using the Suppressive Subtractive Hybridization (SSH) methodology. After cloning, sequencing and gene identification, the genes (1070 clones corresponding to 822 different sequences) were classified according to (1) the subtracted library from which they originated, and (2) within 58 groups of gene functions. We then developed a Logarithm of the Odds (LOD) test in order to identify a possible excess of genes in each group. We show that genes involved in angiogenesis are significantly over-represented in the "hypoxic" condition (2% O₂), while apoptotic genes are over-represented in the "normoxic" condition (20% O₂). Furthermore, we observed an excess of kinases relative to phosphatases and an excess of genes involved in proliferation over genes involved in cell growth in the "hypoxic" condition. To validate our results, we used quantitative RT-PCR to analyze the set of 8 genes involved in angiogenesis on 9 independent placentas. Finally, we studied the distribution of gene clusters on human chromosomes to check whether their chromosomal distribution was random or not. We observed on HSA11 a clear clustering of genes regulated similarly by O₂ tension, and we also discovered indications that such clustering exists on chromosomes 6 and 12.