Myelination up to the age of 6 years was studied in two groups consisting of 129 Down syndrome (DS) 17/129 fetuses and 112/129 postnatal) and 73 non-DS cases (10/73 fetuses and 63/73 postnatal). In both groups studied a similar number of congenital heart disease (CHD), gastrointestinal (GI) malformations and infections were diagnosed. Paraffin or celloidin brain sections were stained with Klüver-Barrera, Heidenhain or Loyez method. The myelination was found to be delayed in 29/129 (22.5%) DS and only in 5/73 (6.8%) non-DS cases. Myelination in fetuses and newborns in the DS and non-DS groups was not delayed. In DS the myelination was delayed between ages 2 months-6 years (17/29; 58.6%) up to 12 months, and 12/29 (41.4%) aged 2-6 years, while in non-DS aged 2-6 months only. The myelination delay affected tracts with late beginning and slow cycle of myelination, mainly the associated and intercortical fibers of the fronto-temporal lobes. In 3/7 of DS cases (ages 3, 4, 6 years) less advanced myelination of U fibers was noted. In both groups the myelination delay seemed also to depend on the systemic diseases which affected the subjects during the time of myelination. In DS where CHD was present the myelination delay was found in 14/29 (48.2%) in contrast to 3/5 (60%) non-DS. Also, in 28/129 (23%) DS cases dates regarding the developmental milestones were available and some correlation was found between developmental and myelination delay.(ABSTRACT TRUNCATED AT 250 WORDS)