Forty-eight children with disseminated demyelination of the CNS, 28 with acute disseminated encephalomyelitis (ADEM), seven with multiphasic disseminated encephalomyelitis (MDEM) and 13 with multiple sclerosis were studied for a mean follow-up period of 5.64 years. The presentation findings of the ADEM/MDEM group were compared with those of the multiple sclerosis group. The following findings were more commonly seen in ADEM/MDEM presentation compared with the multiple sclerosis presentations: predemyelinating infectious disease (74 versus 38%, P: < 0.05); polysymptomatic presentation (91 versus 38%, P: < 0.002); pyramidal signs (71 versus 23%, P: < 0.01); encephalopathy (69 versus 15%, P: < 0.002); and bilateral optic neuritis (23 versus 8%, not significant). Seizures occurred only in the ADEM/MDEM group (17 versus 0%, not significant). Unilateral optic neuritis occurred only in the multiple sclerosis patients (23 versus 0%, P: < 0.01). There were no differences in the frequencies of transverse myelitis, brainstem involvement, cerebellar signs and sensory disturbance between the two groups. ADEM/MDEM patients were more likely to have blood leucocytosis (64 versus 22%, P: < 0.05), CSF lymphocytosis (64 versus 42%, not significant) and CSF protein elevation (60 versus 33%, not significant). Patients presenting with multiple sclerosis were more likely to have intrathecal synthesis of oligoclonal bands on presentation (64 versus 29%, not significant). MRI showed that subcortical white matter lesions were almost universal in both groups, though periventricular lesions were more common in multiple sclerosis (92 versus 44%, P: < 0.01). By contrast, in ADEM/MDEM there was absolute and relative periventricular sparing in 56 and 78% of patients, respectively. Follow-up MRI revealed complete or partial lesion resolution in 90% and no new lesions in the ADEM/MDEM group. All of the multiple sclerosis patients had new lesions on repeat MRI (five during relapse and six during asymptomatic convalescent phases). The outcome in the ADEM patients was mixed; 57% of patients made a complete recovery. The mean follow-up for the 35 ADEM/MDEM patients was 5.78 years (range 1.0-15.4 years). Eight of the 13 multiple sclerosis patients relapsed within the first year; 11 had a relapsing-remitting course, one a primary progressive course and one a secondary progressive course. These differences in the presentation of ADEM/MDEM compared with multiple sclerosis may help in the prognosis given to families regarding the possibility of later development of multiple sclerosis.