We searched for the presence of apoptotic cell death and studied the distribution of bcl‐2, an oncoprotein that counteracts apoptosis, in amyotrophic lateral sclerosis (ALS). Brain and spinal cord specimens from 12 ALS patients were compared with those from six non‐neurological controls. ALS brain tissue was pre‐selected by the presence of reactive cortical damage. Apoptosis was demonstrated by in situ end‐labelling of fragmented DNA, a method that is suitable for formalin‐bed, paraffin‐embedded tissue. All ALS patients exhibited some apoptosis, eight of them did so in each of the three central nervous system (CNS)‐levels studied. Apoptosis was not restricted to the motor system, but also affected other neuronal and non‐neuronal CNS elements. Apoptosis corresponded with cell shrinkage, and neuro‐nophagia in Nissl stains and with small Nissl‐positive bodies. None of the non‐neurological controls showed as much apoptosis as any of the ALS cases. Immunocyto‐chemically, the overall distribution of BcI‐2 did not differ between ALS and non‐neurological controls. In ALS, however, we found variable degrees of increased Bcl‐2 expressed in the nuclei and in the cytoplasm. We found no inverse relationship between apoptosis and bcl‐2 expression.