A B S T R A C T Acidic solvenits extract the same porphyrin-protoporphyrin-from the erythrocytes of patients with either erythropoietic protoporphvria or lead intoxication. However, extractable protoporplhyrin disappears rapidly, both in vivo alnd in vitro, frolmi ervthrocytes in erythropoietic protoporphyria but slowly, if at all, in lead intoxicationi. Consistent w-ith these observations, fluorescence spectroscopy revealed that the intracellular state of the erythrocyte protoporphyrin is different in the two diseases. Spectrofluorometric measurements coupled with fractionations and biochemical syntheses showed that in erythropoietic protoporphyria the protoporphyrin is bound as the free base to lhellmoglobin molecules at sites other than the heme bilnding sites. In lead intoxication the fluorescent porphyrin is also bound to hemoglobin but is present as zinlc protoporphyrin. The data suggest that the zilnc protoporphyrin is bound at heme binding sites. Acidic extraction solvents remove the chelated zinc, but zinlc protoporphiyrinl may be extracted intact from erythrocytes w-ith acetone, ethaniol, or the detergent Ammnonyx-LO.