A hypothesis has been proposed that claims much of the phenomena of decompression sickness (DCS) are mediated by the complement system of blood plasma. This "complement hypothesis" can be used to explain the variation in susceptibility of individuals to DCS, including the phenomena of acclimatization and de-acclimatization. In this study, certain predictions of the complement hypothesis were examined by exposing rabbits to a particular pressure profile; some were observed to have symptoms of DCS and some showed none. Those that were observed to have symptoms were also found to have native complement systems that were activated by air bubbles, and those that did not show symptoms of DCS when exposed to the same pressure profile had native complement systems that were not activated by air bubbles. Rabbits that had shown symptoms of DCS the first 2 times that they were exposed to the pressure profile could be acclimatized to the pressure profile by pharmacologically decomplementing them in vivo. After being decomplemented, they showed no symptoms of DCS when they were exposed to the same pressure profile for a third time. When the decomplemented rabbits were allowed to remain inactive for a period of time that was sufficient to allow their complement systems to return to normal, after having been decomplemented, and were then subjected to the pressure profile for the fourth time, they were each again observed to have symptoms of DCS, i.e., they became de-acclimatized when their complement systems had returned to their native sensitivity. These results provide further experimental support for the complement hypothesis.