Human squamous cell carcinoma cells cloned from the hypopharynx (FaDu) and oral cavity (SCC-4) were exposed to high-energy pulsed ultrasound (HEPUS) in vitro to evaluate the effects of various physical parameters on cell viability. Such included the number of pulses, voltage applied, pulse repetition rate and cell density. The experimental piezoelectric ultrasound transducer used in the experiments generated pulses with a high negative pressure amplitude. By varying the repetition frequency from 0.6 to 8 Hz, cell viability was found to be least when pulse repetition was approximately 1 Hz. An increase in transducer voltage resulted in a linear decrease in cell viability. The cell survival rate dropped exponentially as a function of the number of pulses applied, reaching 4.2% after 2000 pulses. The cell survival rate exhibited no significant dependence on cell density when cells ranged from 1 to 3.5 x 10(6) cells ml-1. Data obtained with trypan blue dye exclusion were confirmed by measurements of intracellular lactate dehydrogenase released into an extracellular fluid supernatant. By applying HEPUS to tumor cells, almost complete destruction of the cells could be achieved in vitro. The degree of cell destruction achieved depended significantly on the number of pulses administered, the pulse repetition rate and the transducer voltage applied.