The active component(s) in yeast extract required by Thermoplasma acidophilum for growth is polypeptide in nature. A fraction from yeast extract was isolated and partially characterized as one or more peptides of molecular weight about 1,000 containing 8 to 10 amino acids. Although it was composed largely of basic and dicarboxylic amino acids, only one amino group per molecule was free. The polypeptide(s) appeared to bind avidly to cations. No other organic compounds except glucose were needed by Thermoplasma. Among several hundred known compounds tested, only glutathione plus Fe2+ or Fe3+, clostridial ferredoxin, and spinach ferredoxin elicited any growth response.