Many factors affect the sensitivity and reliability of tumor vasculature assessment at the small doses of contrast agent necessary for imaging mice. In this study we investigate the dose-response relationship of ultrasound contrast agent for a minimal exposure power Doppler technique (minexPD) in a murine melanoma model. K1735 murine melanomas grown in 25 C3H/HeN mice were imaged by power Doppler ultrasound using different doses of contrast agents, Optison(R) and Definity(R). Six mice were treated with an antivascular agent, combretastatin A4-phosphate (CA4P), and imaged before and after treatment. The color-weighted fractional area (CWFA) of the peak-enhanced image was measured to assess tumor perfusion on a relative scale of 0 to 100. CWFA increased logarithmically with dose (R(2)=0.97). Treatment with CA4P resulted in pronounced reduction in tumor perfusion 2 h after contrast injection, but perfusion recovered in the tumor periphery after 2 days. CWFA was significantly different between pre- and post-treatment for all doses at 2 h and 2 days (p < 0.05, respectively). There was no significant difference detectable between the two contrast agents, Optison(R) and Definity(R) (p = 0.46). In vivo tumor enhancement in mice increases as logarithmic function with dose. Although the extent of enhancement is dose dependent, the difference between pre- and post-therapy enhancement is relatively unchanged and uniform at varying doses. The two contrast agents tested in this study performed equally well. These results suggest that quantitative contrast-enhanced power Doppler imaging is an effective method for monitoring therapy response of tumors in mice.