To explore the involvement of apoptosis in the development of oral and oropharyngeal squamous cell carcinoma (SCC) in vivo, biopsies were taken from patients with macroscopically normal (n = 6), leukoplakic (n = 12) or malignant (n = 8) mucosa. Leukoplakic lesions were divided histologically into dysplasia (n = 5) or carcinoma in situ (CIS: n = 7). Material was prepared for light and electron microscopy. The apoptotic index (AI), vertical cell position of apoptoses (cp), mitotic index (MI) and AI:MI ratio were calculated for each patient. AI increased from 0.12% +/- 0.07 S.E.M. (normal) to 0.58 +/- 0.13 (CIS) but fell to 0.14 +/- 0.14 in SCC. Apoptoses were suprabasal in normals, but generalised in CIS. MI increased from normal (0.20 +/- 0.06) to SCC (0.32 +/- 0.09), and AI:MI was at its maximum in CIS (1.57; SCC: 0.44). The results suggest that a change in apoptosis accompanies the onset of invasion in a premalignant lesion of the human oral cavity and oropharynx.