AbstractComplexin 1 (CX1) and complexin 2 (CX2) are presynaptic proteins that modulate neurotransmitter release and are used as markers of inhibitory and excitatory synapses, respectively. The aim of this study was to gain insight into the development of inhibitory and excitatory synapses in human prefrontal cortex (PFC) by examining the expression of CX1 and CX2 in postmortem tissues. Relative complexin protein levels were measured by Western blotting in postmortem dorsolateral prefrontal cortex (DLPFC) of 42 subjects without neurological or psychiatric disease ranging in age from 18 gestational weeks to 25 years. Samples were batched a priori into fetal, 0–12 month, 1–5 years, 6–10 years, 11–15 years, 16–20 years, and 21–25 years age groups. CX1 and CX2 expression and CX2/CX1 demonstrated a significant effect of age group by ANOVA. Group CX1 level increased progressively across development and was lowest in the fetal group and highest in the young adult group, whereas group CX2 level increased between the fetal and the 6–10 years groups and then plateaued. Consistent with these divergent patterns, there was a significant effect of age group on CX2/CX1, which was higher in fetal and infant groups than in the young adult group. Furthermore, regression analysis demonstrated linear relationships of CX1 and CX2/CX1 with age, whereas CX2 was better described as having a curvilinear relationship with age. These data indicate that complexin expression increases during synaptic maturation in human DLPFC and that an increase in the influence of inhibitory synapses relative to that of excitatory synapses occurs during development in this cortical region. Synapse 62:273–282, 2008. © 2008 Wiley‐Liss, Inc.