Studies of naturally-acquired immunity to malaria in endemic regions provide the potential for a greater understanding of the regulation of human immune responses to the malarial parasite. However, little is known about the acquisition of malaria-specific immunity in regions of unstable, meso-endemic or hypo-endemic transmission. Cytokine profiles - patterns in the expression of interleukin-4 (IL-4), interleukin-10, interleukin-12, interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) - were therefore studied during the natural acquisition of immunity to Plasmodium falciparum and P. vivax among individuals from Buenaventura, a meso-endemic region on the Pacific Coast of Colombia. In general, specific type-1 immune responses, characterized by IFN-γ expression, were more likely to develop during P. falciparum infection, whereas pro-inflammatory cytokine profiles (with TNF-α expression) were observed more frequently among the P. vivax infections. Type-2 cytokine profiles, characterized by dominant IL-4 expression, were infrequent. Expression of IL-4 probably occurs primarily after prolonged exposure to parasites (which would, by definition, not be common in a meso-endemic region).