The size and shape characteristics of permanent mandibular first molars were compared in a group of young males with Down syndrome (DS) and a control group of normal males. Generalized size was quantified by the log transforms of five intercusp distances and shape by a principal component analysis of the log distances scaled to constant size. On average the DS molars were smaller than the controls by 8%, the most marked reduction being in the distance between the distal and distolingual cusps. The scores on two of the four components of shape also differed between the DS and control teeth. These two shape components, which accounted for over 41% of the total shape variation, were determined specially by the occlusal morphology of the distal crown region. Discriminant function analyses also indicated the importance of the distal regions in discriminating between control and DS molars. Evidence suggests that trisomy 21 is associated with a general retardation in growth. The observed features of DS molars were consistent with decreased cellular activity in the developing tooth germs, producing morphological changes that were more pronounced in the later-forming crown regions.