Lysophospholipids are metabolic intermediates in phospholipid turnover, detergent molecules with membrane-modulating effects, and multifunctional cellular growth factors in eukaryotic cells. In bacterial cells, lysophospholipids are mostly found in the form of lysophosphatidylethanolamine. We show that a heat shock from 30 to 42degreesC increases four-fold the Escherichia coli pool of lysophosphoethanolamine and that lysophospholipids display chaperone-like properties. Lysophosphatidylethanolamine, like molecular chaperones such as DnaK, promotes the functional folding of citrate synthase and a-glucosidase after urea denaturation. Like chaperones, lysophophatidylethanolamine, lysophosphatidyleholine, lysophosphatidylinositol and lysophosphatidic acid prevent the aggregation of citrate synthase at 42degreesC. The renaturation and solubilisation of proteins by lysophospholipids occur at micromolar concentrations of these compounds, close to their critical micellar concentration. Furthermore, lysophosphatidylethanolamine is much more efficient than other detergents tested for the renaturation and solubilisation of citrate synthase. In contrast with lysophospholipids, phosphatidylethanolamine and phosphatidyleholine are not able to promote citrate synthase folding nor to prevent its aggregation at 42degreesC. The chaperone-like properties of lysophospholipids suggest that, in addition to their known functions, they might affect the structure and function of hydrophilic proteins.