Air-filled microbubbles are in clinical use as echo-contrast agents for sonographic applications. The synthesis of aqueous suspensions of air-filled proteinaceous microbubbles involves the ultrasonic irradiation of aqueous protein solutions in the presence of O2. Yields and size distributions of human and bovine serum albumin microbubbles have been determined as a function of various experimental parameters. The chemical nature of these microbubbles and the origin of their remarkably long lifetimes have been explored. The microbubbles are held together primarily by interprotein cross-linking of cysteine residues. The principal cross-linking agent is superoxide created by the extremely high temperatures produced during acoustic cavitation.