In order to evaluate the relationship between fever and macrophage activation in vivax malaria, serum interferon-gamma (IFN-gamma) and urinary neopterin concentrations were determined in Thai adults with Plasmodium vivax parasitaemia. Magnitude of fever, after controlling for parasite density, was found to be positively correlated with both IFN-gamma (r = 0.47) and neopterin (r = 0.57). In the 26 febrile patients, neopterin excretion increased further during the first two days of chemotherapy (P = 0.0002). Mean neopterin values for both groups had fallen to within the normal range by the sixth day post-treatment. Thus, the fever of vivax malaria was associated with IFN-gamma induced macrophage activation, as reflected by neopterin excretion.