Several mechanisms involving oxygen conservation or increased blood gas storage capacity serve to facilitate prolonged diving in mammals. Two such mechanisms present in humans are the cardiovascular �diving response� and the blood boosting spleen contraction. Repeated diving may elicit these adaptive responses by similar or different mechanisms. Increased hematocrit (Hct) attributable to spleen contraction raises blood gas storage capacity during human apneic diving or simulated diving, but the underlying mechanisms have not been clarified. The time course for development of the Hct response is slower than for the cardiovascular diving response: The development of spleen contraction is progressive across 3 serial apneas, and recovery takes 8-9 minutes. Also, while the diving response is initiated by apnea and fortified by facial chilling, the stimulus eliciting Hct increase is related to apnea alone. Thus apnea itself or its consequences appear to be the main stimulus. In this study we focused on the role of hypoxia in triggering spleen induced elevations in Hct. After horizontal rest for 20 min, nine volunteers performed 3 maximal apneas spaced by 2 min of rest, preceeded by an inspiration of normal air. The series was repeated at a different day using the same apneic durations but after 60 s of 100% oxygen breathing and oxygen inspiration prior to apneas. Relative to pre-apnea values, the post apneic arterial oxygen saturation nadir averaged 84% after the air trial and 99% after the oxygen trial. The Hct rose in both protocols, but with about twice the magnitude after apneas with air. A relative increase of 2.7% was found after three apneas with air (p<0.01), and 1.4% increase after three apneas with oxygen (p<0.05). Values returned to pre-apneic levels within 10 minutes. We conclude that hypoxia may be an important modifying factor influencing the magnitude of hematocrit increase during apnea.