The demonstration of parasites in peripheral blood by microscopy, RDT, or PCR is the defining evidence of infection by the plasmodia. Negative findings lead us to accept the absence of malaria, though we understand that clinically silent sub-patent or latent infections may be present. In rare instances we encounter acute and chronic disease states with negative findings by peripheral blood examination that later prove positive for P. vivax by bone marrow biopsy or splenectomy. A great deal of new evidence suggests the rarity of such cases may be in the invasive diagnostic work-up rather than the state of infection. Tropisms of P. vivax away from peripheral blood and toward extravascular spaces of bone marrow, spleen (and perhaps the liver and other tissues where extramedullary hematopoiesis may occur) supports the plausibility of active, disease-causing/transmissible vivax malaria with very low-grade, transient, and improbably detected parasitemia. How common such a state of infection may be is wholly unexplored and unknown. This question may be especially relevant in Duffy-negative Africa where active transmission of P. vivax is occurring despite infrequent and uniformly very low-grade infections of peripheral blood. The few serological studies of P. vivax in that region consistently point to much higher prevalence of the infection than conventional diagnostics seem to infer. This research community should consider the plausibility of active P. vivax malaria without peripheral blood parasitemia as a common state of infection.