Apoptosis as introduced by Kerr and colleagues describes a distinct set of morphological features that represent programmed cell death. Apoptosis frequently arises owing to genetic programming, cytotoxic drugs and physical stimuli. In order to ascertain whether all of the natural triggers of apoptosis have been identified, we looked for the presence of apoptotic cells in all routine blood films throughout a 5-month period. Patients with known malignant disease or on chemotherapy were excluded from the study. Forty-nine blood films, from 10,000 examined in this period, showed apoptosis. The number of apoptotic cells ranged from the occasional cell to 20%. Apoptotic cells were either mainly lymphoid (34 of 49) or mainly myeloid (15 of 49). All 34 cases with lymphoid apoptotic cells were seen in patients with suspected infectious mononucleosis (IM). In patients with IM, the presence of large numbers of apoptotic cells was associated with a prolonged, severe clinical course. Myeloid apoptotic cells were found in a variety of conditions, including one patient who had persistent apoptosis and was found to have myelodysplasia. Unexplained persistent apoptosis in blood films requires further investigation.