We have demonstrated the presence, in the plasma of several patients with acute intermittent porphyria, of a substance which strongly induced the synthesis of porphyrins in chick embryo liver cells growing in primary culture. The induction response evoked by this humoral agent was in all respects similar to that elicited by drugs and hormones which are known to enhance porphyrin production by inducing the de novo formation of delta-aminolevulinate synthetase, the rate-limiting enzyme in this pathway. Inducing properties were not found in the plasma of normal individuals or in that from porphyric patients in remission. Significant inducing activity was, however, found in the plasma of some normal subjects ingesting drugs or contraceptive steroid mixtures. The occurrence of a potent inducer of delta-aminolevulinate synthetase in the plasma of certain porphyric patients may have clinical significance for these genetically susceptible individuals. It will also permit chemical characterization of those humoral agents which may be related to the episodic exacerbations of this hereditary liver disease.