Characteristics of the humoral immune response of Cooperia oncophora-infected calves to low molecular weight antigens of C. oncophora were studied. Immunoblotting with sera obtained from calves 6 weeks after a single oral infection with 100,000 third-stage (L3) C. oncophora larvae revealed several corresponding antigenic fragments between adult worms and the fourth-stage (L4) larvae. No reactivity in the immune sera was found against the L3 stage. A previously defined complex of low molecular weight proteins (12-15 kDa) was found on both L4 and adult Cooperia stages, but not on the L3 stage. C. oncophora adults differed from the L4 larvae at the 31/32 and 37 kDa level. Several adult and L4 proteins were bound by biotinylated Concanavalin A, as was also true for L3 proteins. A 31/32 kDa glycoprotein of adult worms was recognised by a monoclonal antibody with specificity for phosphorylcholine. Using monoclonal antibodies in ELISA and Western blotting, the serum antibody response of C. oncophora-infected calves to adult worm antigen was almost entirely IgG1. Binding of the IgG1 antibodies was restricted to a complex of reduced 12-15 kDa protein(s) and a 27 kDa fragment of adult worms. The data suggest that the systemic humoral immune response of calves during a primary infection with C. oncophora consists mainly of an IgG1 response, and is directed to a non-glycosylated Cooperia protein (molecular weight estimated at 12-15 kDa under reducing conditions and 18 kDa under nonreducing conditions). This protein is probably present in both L4 larvae and adults. Since it was not bound by immune sera from calves mono-infected with several other nematodes, the 12-15 kDa protein complex may represent a Cooperia-specific component that can be used for serodiagnosis.