The 1 1 MHz ultrasound response of micrometer-scale perfluorbutane gas bubbles, coated with a mixture of 90 mol % saturated phospholipid (disteroylphosphatidylcholine, DSPC) or unsaturated phospholipid (dioleoylphosphatidylcholine, DOPC) and 10 mol % PEG-lipid, was studied by optical microscopy Uncoated bubbles were also studied Bubbles, Jesting buoyantly against the wall of a polystyrene cuvette, were exposed to brief pulses of ultrasound (similar to 200 kPa amplitude) at a repetition rate of 25 Hz. images of the bubbles were taken after every other pulse The coating had little effect on the initial response large (> 10 mu m diameter) bubbles showed no size change, while smaller bubbles rapidly shrank (or fragmented) to reach a stable or metastable diameter-ca 2 mu m lot coated bubbles and 4 mu m for uncoated bubbles The coating had it significant effect on further bubble evolution. after reaching a metastable size. uncoated bubbles and DOPC-coated bubbles continued to shrink slowly and ultimately vanished entirely. while DSPC-coated bubbles did not change perceptibly during the duration of the exposure Numerical modeling using the modified Herring equation showed that the size range in which DSPC bubbles responded does correspond well with the bubble resonance, the long-term stability of these bubbles may he related to the ability of the DSPC to form a two-dimensional solid at ambient temperature or to phase separate from the PEG-lipid