A new procedure, the radioimmunoprecipitation-PEG assay (RIPEGA) is proposed for the quantitation of total circulating schistosome antigens (CSA) and circulating antigen '4' in patients, mice and rats infected with Schistosoma mansoni. This sensitive and reproducible method was performed by incubation of [125I]anti-S. mansoni rabbit antibodies (for the detection of CSA) or [125I]anti-antigen '4' antibodies (to detect antigen '4') with sera. Separation of free from complexed antibodies was achieved by a 7% polyethylene glycol (PEG) precipitation. In human schistosomiasis, both CSA and antigen '4' were detected. A direct relationship was observed between S. mansoni egg output and the incidence of CSA. Moreover, all the patients with more than 500 eggs/g stool showed antigen '4' in serum. Both CSA and antigen '4' were also detected during the course of S. mansoni infection in mice. CSA was increased in two distinct periods after infection; the first between the 50th and the 70th day and the second after the 80th day of infection. The antigen '4' became detectable in infected mice after 45 days of infection. In rat schistosomiasis, only CSA was studied. It was demonstrated in two distinct periods after infection, between the 4th and the 6th week and between the 11th and the 14th week. Because of its sensitivity and its ability to detect and quantify CSA and circulating antigen '4', the RIPEGA is recommended for the clinical studies of schistosomiasis.