The urinary and faecal porphyrin excretory profiles of dual porphyria are said to represent the superimposition of those found in porphyria cutanea tarda on those seen in variegate porphyria. To test this hypothesis the enzymes responsible for these conditions, protoporphyrinogen oxidase (variegate porphyria) and uroporphyrinogen decarboxylase (porphyria cutanea tarda) were measured in vitro in haemolysates and lymphoblasts of 10 subjects with dual porphyria in order to clarify the enzymatic defects. Mean protoporphyrinogen oxidase activity in lymphoblasts from subjects with dual porphyria was decreased by 45% from 0.82 +/- 0.10 to 0.45 +/- 0.09 nmol protoporphyrin/mg protein/h (P less than 0.001). Uroporphyrinogen decarboxylase activity was also significantly reduced from 0.12 +/- 0.05 nmol 7-, 6-, 5- and 4-carboxyl porphyrin/mg protein/h in lymphoblasts from normal subjects to 0.08 +/- 0.02 nmol in lymphoblasts of subjects with dual porphyria (P less than 0.01). There was a similar 27% decrease in mean uroporphyrinogen decarboxylase activity of haemolysates from the same dual porphyria group (P less than 0.01). Mean activity of this enzyme in 5 patients with variegate porphyria did not differ significantly from that in normal subjects. These findings may well provide a rational basis for the abnormal porphyrin excretory profiles found in subjects with dual porphyria.