Circulating antigen of schistosomal origin (Schistosoma mansoni) can be detected in sera from infected animals by complement fixation (CF). Rabbit antisera employed in the CF reaction were prepared by immunization with antigen extracted from whole worms which was purified and concentrated by starch-block-electrophoresis and ultrafiltration. Concentrated antigen was complexed with methylated bovine serum albumin before emulsification with adjuvant and use as an immunogen. By gel diffusion, the rabbit antisera detected a single antigen in extracts of adult worms and in sera from hamsters heavily infected with Schistosoma mansoni. The sensitivity of detection of circulating antigen by CF as compared to gel-diffusion was increased many-fold. Circulating antigen could be detected in the sera of some hamsters infected with 800 cercariae as early as the 18th day after infection. Titers of circulating antigen were assayed by CF during the 6-week period after infection. Two patterns were revealed. In 75% of infected animals titers rose steadily from time of detection; in 25% titers rose and then plateaued after the 32nd to 35th day. A direct relationship was demonstrated between the titer of antigen and the worm burden in infected hamsters between the 4th and the 7th weeks of infection. Using the CF reaction, antigen with properties of circulating antigen was not detected in egg extracts.