Delivering ultrasound to HeLa cells at 1 MHz using a high frequency pulse regime (40 kHz) and at a maximum energy density of 270 Jcm(-2) resulted in significant cell membrane permeabilisation. Using FITC-dextran as a fluorogenic marker.. optimally up to 64% of treated populations were permeabilised with cell viability remaining above 80%. Although cell membrane permeabilisation was observed in the presence of the microbubble-based ultrasound contrast agent, SonoVue (R), cell viability was severely compromised. Using the high frequency pulse regime in the absence of microbubbles, the LD50 of the cancer chemotherapeutic agent, camptothecin, was reduced from 58 to 18 nM. (C) 2008 Elsevier Ireland Ltd. All rights reserved.