Lysates of Plasmodium falciparum parasitized human erythrocytes stimulate U937 cells to secrete neopterin during a 48hr co-culture period. Neopterin secretion by U937 cells was enhanced by the addition of human interferon gamma (IFN-γ). Several P. falciparum antigens, ‘FC27’ (a synthetic ‘S’ antigen), Ag16 (a recombinant ‘S’ antigen) and Ag44/RHOP3 (a recombinant merozoite rhoptry protein), also activated U937 cells to neopterin secretion and produced a similar effect on peripheral blood mononuclear cells (PBMC) from 2 of 3 normal healthy donors cultured with the antigens for 7 days. Plasma from six Nigerian malaria patients contained high neopterin concentrations ranging from 5.06 to 14.17ng/ml. This preliminary pilot study lends support for further investigation incorporating a larger number of malaria patients and further culture experiments with U937 cells and PBMC with the aim of defining the cause and source of the large quantities of plasma neopterin produced in this infection.