Daphnia: Hemoglobin synthesis in the crustacean Daphnia magna is induced by declining pO2 and juvenile hormones. Focusing on Daphnia's strongly up-regulated globin gene #2 (hb2), two hypoxia-response elements (HREs), once bound by hypoxia-inducible factors (HIF), and one juvenoid response element (JRE) were found within the gene's promoter to contribute in adjusting metabolic and reproductive O2 demands via hb2 synthesis. Drosophila: To understand, on a genomic level, the remarkable ability of many invertebrates to survive severe and prolonged deprivations of oxygen, Drosophila's hypoxia tolerance was analysed through microarray and Northern blot surveys of embryonic fly cells (SL2). HIF-expressing SL2 cells were kept as normoxic controls (15–16% oxygen in medium) or challenged by graded hypoxia (16h at 4% or 1% or 0.2% oxygen), thus approximately representing oxyregulatory, aerobe/anaerobe-transitory and metabolically depressed physiological states, respectively. Increasing severity of the hypoxic stress (4%®0.2% O2) was reflected in rising numbers and magnitudes of hypoxia-responsive gene regulations. With few exceptions, mild hypoxia (4% O2) lacked normoxia-deviating gene responses, pointing to a global homeostasis during Drosophila's aerobic metabolism. In contrast, 1% and 0.2% O2 expression profiles revealed, often HIF-mediated, regulations to progressively reduce ATP-costly protein synthesis and cell proliferation.