Pb2+ activated native chick-embryo liver mitochondrial delta-aminoaevulinate synthase (EC 2.3.1.37). This result contradicted with the inhibitory effect observed by earlier workers who used degraded enzyme preparations. Enzyme activation was biphasic. An initial activation phase was observed with Pb2+ concentrations up to 200 microM, and a secondary phase with concentrations from 200 microM to at least 2mM. Maximum primary activation was 2.5-fold at 200 microM-Pb2+, with a further 2-fold activation observed at 2mM-Pb2+. Primary activation was not affected by a 10-fold molar excess of dithioerythritol, but the secondary activation was abolished by dithioerythritol. Secondary-phase activation was lost upon increasing time of incubation of the enzyme with Pb2+. The implications of these findings are discussed with reference to lead poisoning and the mechanism of delta-aminolaevulinate synthase.