To characterize the immune response following primary human hookworm infection, an adult volunteer was infected with 50 L3 larvae of Necator americanus, reinfected 27 months later and followed for a further 6 months. Clinical signs, blood picture, ex-vivo peripheral blood cytokine production (IFN-gamma, IL-5, IL-13, IL-10 to mitogen and hookworm antigen), acute phase proteins (APP) (C-reactive protein, CRP and alpha1-antitrypsin, alpha1-AT) and antibody levels were determined. Dermatitis, oedema, mild nausea and abdominal discomfort followed the primary infection. Eosinophil counts peaked early during both infections but remained elevated ( approximately 18%) throughout. Transient production of IL-5, IL-13 and APP also followed infection but there were negligible levels of IFN-gamma or IL-10. The onset of nausea, oedema and the initial rise in CRP, alpha1-AT, eosinophilia and IL-5 coincided (days 13-27) with the late larval migration and early establishment of the preadult worms in the intestine. Apart from the eosinophilia these responses declined to baseline levels within 4 months and were less pronounced on re-infection.