To determine the effect of ultrasound on hyperthermia-induced apoptosis, we exposed U937 cells (in air-saturated suspension) to continuous 1 MHz ultrasound at intensities 0.5 or 1.0 W/cm(2), considered non-thermal and sub-threshold for inertial cavitation, while at 44.0 degrees C for 10 min. We found that 0.5 W/cm(2), in combination with hyperthermia, synergistically induced apoptosis. On the other hand, 1.0 W/cm(2) in combination with hyperthermia showed an augmented instant cell lysis but no significant change in the ratio of apoptosis. This result might be useful when apoptosis induction is desired over instant cell killing in cancer therapy.