Prototheca richardsi, an unpigmented heterotrophic alga, causes growth inhibition in amphibian larvae and has proved refractory to culture in Vitro. P. richardsi replication is dependent on regular passaging through tadpole digestive systems; uptake of thymidine by free-living Prototheca cells and incorporation into DNA are very low by comparison with leucine uptake and incorporation into protein, but DNA synthesis is detectable in cells isolated from tadpole intestines. DNA replication was elicited 6–8 h after ingestion in protothecans fed to tadpoles and subsequently re-isolated from them, providing that the tadpoles were fed subsequent to the ingestion. It appears that passaging through tadpole intestines provides an essential stimulus to maintaining an active cell division cycle in P. richardsi.