INTRODUCTION: Space flight conditions may influence a variety of physiologic functions of mammals, including muscle, bone, neurovestibular function and the immune response, that is depressed in more than 50% of the astronauts during and after space flights (1). The human studies in microgravity are limited, although some modelling studies have been done. The most common model is chronic bed-rest with a head-down tilt, but many studies have also used water immersion as experimental model that reproduces more closely effects of acute adaptation to simulated weightlessness (2). Stress hormones, specifically growth hormone, prolactin and cortisol, are widely recognized for their ability to alter circulating leukocyte number and function (3) These results suggest that stresses that occur during space flight could combine with microgravity conditions in inducing the changes seen in immune responses after space flight. OBJECTIVE: The aim of this study was to investigate the effects of microgravity and stress responses on immunity, taking advantage on the prolonged diving of two healthy volunteer that stayed for 25 hours in a pool at the depths of 2 meters at room temperature, establishing the new world record of prolonged dive. STUDY POPULATION Two male healthy volunteers (DC, 22 years old, and MB, 26 years old) continuosly stayed for 25 hours in a pool with air respiratory in a hydrostatic equilibrium. The average depths was 2 m. Thirty milliliter of peripheral blood were obtained the day before the prolonged dive and immediately after its conclusion (within 15 minutes). RESULTS: After the dive with respect to the basal determinations we found in both the subjects: an overall increase in WBC and in particular in neutrophil numbers; a significant increase in plasma cortisol, growth hormone and prolactin; a decrease in number of NK cell (CD56+ cells) as determined by flow cytometry analysis; a significant decrease of the T-cell proliferative activity in presence of polyclonal stimulation; a significant decrease of the intracytoplasmic expression of IFN-gamma and a parallel increase of IL-4 levels, suggesting a Th1 versus Th2 switch. There were no significant differences in the cytotoxic activity of NK cells CONCLUSIONS: Our subjects were the first in the world continuously diving for 25 hours. Taken together our data show that the prolonged dive alters the levels of stress hormones and impairs immune system, in particular down-modulating T-cell and the NK-cell subsets, explaining the depression of the immunosurveillance observed in subjects that are maintained in microgravity conditions.