This study evaluates the histopathological changes that follow insonation of a neoplasm with physiotherapy ultrasound. In 27 mice (C3HV/HeN strain), a subcutaneous melanoma (K1735(22)) was insonated with continuous physiotherapy ultrasound (1 MHz; spatial-average-temporal-average = 2.3 W cm(-2)). Analyses of contrast enhanced (0.1 mL Optison) power Doppler observations showed that insonation significantly (p < 0.05) increased the avascular area in the neoplasm. The predominant acute effect of insonating the neoplasm was an apparently irreparable dilation of the tumor capillaries with associated intercellular oedema; other immediate effects were haemorrage and increased intercellular fluid. Liquefactive necrosis of neoplastic cells was a delayed effect. There was a high correlation (R2 = 0.91) between the percent area affected on histologic examination and the percent increase in avascularity of the neoplasm in the Doppler study. In conclusion, physiotherapy ultrasound produced histologic changes in the tumor vasculature that were consistent with observations made by contrast enhanced power Doppler ultrasound.