The course of zinc protoporphyrin research has progressed at an increasingly rapid pace on several fronts. A variety of biochemical and clinical evidence viewed in toto now suggests that ferrochelatase catalyzes zinc protoporphyrin formation in states of relative iron-deficient erythropoiesis and in lead-inhibited iron metabolism. Furthermore, a redefinition of the relationship of zinc protoporphyrin to certain other parameters of iron status has been made based upon changes during the earliest states of iron depletion. These clinical studies show that the zinc protoporphyrin level and the ferritin level vary in concert but that changes in the percent transferrin saturation and in the hematocrit results are less consistent. Thus zinc protoporphyrin and ferritin are closely linked metabolically such that iron-deficient erythropoiesis becomes an initial manifestation of iron depletion. The measurement and expression of results as mumoles zinc protoporphyrin/mole heme have improved the quality of results, partly by the elimination of the assumed hematocrit designed into existing instruments. Other refinements in hematofluorometry technology have permitted exploration of the potentially extensive applications of zinc protoporphyrin measurements for lead surveillance and diagnosis, blood banking, pediatrics, obstetrics, sports medicine, and other clinical situations where a very sensitive, cost-effective indication of iron status is required.