Abstract Objectives: Investigation of the metabolism of the four urinary coproporphyrin isomers I–IV in the extremely rare 5-aminolevulinic acid dehydratase (ALAD) deficiency porphyria (syn.: Doss porphyria), in acute lead intoxication, and after oral 5-aminolevulinic acid (ALA) loading. Design and methods: We analyzed the excretion of total urinary coproporphyrins and the composition of the respective isomers I–IV with ion-pair HPLC methods in these conditions. Results: The concentration of total coproporphyrins was about 30-fold increased in patients with ALAD deficiency porphyria and acute lead intoxication as compared with controls. In addition, the proportion of coproporphyrin III as well as that of the atypical isomers II and IV were significantly elevated at the expense of isomer I. After oral ALA administration to normal volunteers, a 10- to 15-fold increase in the maximal concentration of total urinary coproporphyrins was observed within 12 to 24 h. Urinary levels were back to normal after another 24 h. The excretion pattern of the individual urinary coproporphyrin isomers I–IV after ALA ingestion revealed a dynamic process: initially isomer III was preferentially formed, followed by a 3-fold increase of isomers II and IV via non-enzymatic rearrangement of isomer III, and finally normalization of all four isomers occurred within 48 h. Conclusions: These results demonstrate that oral ALA loading can be used as an in vivo model to study the metabolism of the four urinary coproporphyrin isomers I–IV especially in ALAD deficiency porphyria and in acute lead poisoning.