During exercise in highly-trained older master athletes (MA), the impairment of pulmonary gas exchanges has been shown to be associated with a concomitant increase in histamine release(2). To determine the role of the histamine released (% H) during exercise-induced hypoxemia, seven MA (age 63.2 yr ± 1.9), all of whom were known to develop exercise-induced hypoxemia, performed two maximal incremental exercise tests at a one-month interval after administration of nedocromil sodium (which inhibits histamine and other mediator release) or placebo in random double-blind order. During exercise testing, blood samples for arterial blood gas analysis and histamine assay were drawn at rest, exercise and recovery. Nedocromil sodium induced an inhibition in% H (0.57 ± 0.03 at maximal load (Pmax) with placebo vs 0.24 ± 0.02 with nedocromil sodium) linked with an improvement of pulmonary gas exchange (PaO2: 71.1± 1.4 at Pmaxwith placebo vs 83.4 ± 3 with nedocromil sodium: D(Ai-a)O2: 37.5 ± 1.4 at Pmaxvs 19.1 ± 3.1, respectively). These results confirm the link established between the increase in histamine and exercise-induced hypoxemia in master athletes.