We analyzed the dendritic differentiation of layer IIIc pyramidal neurons of prefrontal cortex (prospective area 9) in the brains of a premature infant and a 2.5-month-old infant with Down syndrome and two age-matched control subjects during the peak period of dendritic growth and differentiation. Our quantitative analysis supports qualitative observation and revealed no significant differences in the tempo and mode of dendritic differentiation between normal and Down syndrome cases. Thus we have concluded that the children with Down syndrome from our study begin their lives with morphologically normal layer III pyramidal neurons. Our findings suggest that pathologic changes of key prefrontal input-output neuronal elements begin to develop in Down syndrome after 2.5 months of postnatal age.