Oscillations of intracellular free Ca2+ concentration are an essential component of the oocyte response to the fertilizing spermatozoon. Ca2+ oscillations have also been observed in human oocytes fertilized by intracytoplasmic sperm injection (ICSI), but only after a considerable delay. The present study was performed to determine whether or not the development of Ca2+ oscillations in sperm-injected oocytes is influenced by exposure of the oocytes to Ca2+ ionophore. The treatment (5 min) of sperm-injected, but not sham-injected, oocytes with 10 microM ionophore A23187 augmented significantly the percentage of oocytes that developed Ca2+ oscillations and accelerated the onset of the oscillations as compared to the values for solvent-treated controls. However, the oscillations developed only after a lag period, which ranged between 25 min and 88 min after the removal of ionophore, during which intracellular Ca2+ levels returned nearly to the basal value. Each of the subsequent periodic Ca2+ rises was initiated from a focus in the oocyte cortex and spread throughout the ooplasm as a Ca2+ wave. These data suggest that ionophore treatment supports the physiological pattern of oocyte activation when applied after ICSI. This effect is probably indirect, implying the stimulation of an unknown process continuing during the lag period.