Anecdotal experience with full blood count (FBC) technology incorporating analysis of depolarized laser light (DLL) for the enumeration of eosinophils showed that malaria infection generated unusual distributions in the white cell channels. The objective of this study was to identify and define criteria for a diagnosis of malaria using this technology. To determine sensitivity, specificity, and positive and negative predictive values, 224 directed samples referred specifically for malaria were used; true positives were defined as those in which malaria was identified by microscopic and/or immunological methods. For the DLL method, positive was defined as one or more large mononuclear cell(s) for which the 90 degrees depolarized signal exceeded the 90 degrees polarized signal. To determine possible utility in a routine haematology laboratory setting, 220 random undirected FBC samples were evaluated for possible malaria infection by the DLL method. Of the 224 directed samples, 95 were malaria positive as determined by microscopic and/or immunological methods, and 129 were negative. For the DLL method, overall sensitivity was 72% (90% in the case of Black Africans), and specificity 96%. Positive and negative predictive values overall were 93% and 82% respectively. In the utility study a single positive result was identified among the 220 samples studied. This was found to be from a patient with malaria. The detection of unexpected malaria by automated screening FBC analysis could substantially lower the mortality and morbidity from unascertained infection, especially in indigenous African peoples.