Healthy Gambian children, children with clinical Plasmodium falciparum malaria, and children with asymptomatic P. falciparum infections were studied to investigate whether antitoxic activities may contribute to protection against malarial symptoms. Markers of inflammatory reactions, soluble tumor necrosis factor receptor I, and C-reactive protein were found in high concentrations in children with symptomatic P. falciparum malaria compared with levels in children with asymptomatic P. falciparum infections or in healthy children, indicating that inflammatory reactions are induced only in children with clinical symptoms. Concentrations of soluble tumor necrosis factor receptor I and C-reactive protein were associated with levels of parasitemia. We detected antitoxic activities in sera as measured by their capacity to block toxin-induced Limulus amoebocyte lysate (LAL) activation. Symptomatic children had decreased capacity to block induction of LAL activation by P. falciparum exoantigen. The decreased blocking activity was restored in the following dry season, when the children had no clinical malaria. Symptomatic children also had the highest immunoglobulin G (IgG) reactivities to conserved P. falciparum erythrocyte membrane protein 1 and "Pfalhesin" (band #3) peptides, indicating that such IgG antibodies are stimulated by acute disease but are lost rapidly after the disease episode. Half of the children with symptomatic infections had low levels of haptoglobin, suggesting that these children had chronic P. falciparum infections which may have caused symptoms previously. Only a few of the children with asymptomatic P. falciparum infections had high parasite counts, and antitoxic immunity in the absence of antiparasite immunity appears to be rare among children in this community.