The authors characterized the effect of intravenous lipid-coated microbubbles (LCMs) on the echogenicity of malignant liver tumors. Novikoff hepatoma cells were inoculated into the livers of 16 anesthetized Sprague-Dawley rats. Sonograms were obtained weekly after tail-vein injection with either 0.2 mL/kg LCMs or saline control. A statistically significant difference in the signal-to-noise ratio (SNR) was observed between the group that received LCMs (10 rats) and the group that received saline (6 rats) (P < .01). The effect persisted for 30 minutes after contrast injection. Selective leakage and accumulation of LCMs into the tumor tissue itself was confirmed histologically using lipid-specific counterstains. Intravenous injection of the LCM contrast agent produces a rapid increase in the echogenicity of the experimental Novikoff tumor in the rat liver.