xũ I sLxxJ In monkey prefrontal cortex, the intrinsic axon collaterals of supragranular pyramidal neurons extend horizontally for considerable distances through the gray matter and give rise to stripe-like clusters of axon terminals (Levitt et al. [1993] J. Comp. Neurol. 338:360-376). Because understanding the functional role of these connections requires knowledge of their synaptic targets, we made injections of biotinylated dextran amine (BDA) into layer 3 of macaque prefrontal area 9 and examined the labeled intrinsic axon collaterals by electron microscopy. Labeled axon terminals formed exclusively asymmetric synapses, and 95.6% of the postsynaptic structures were dendritic spines, presumably belonging to other pyramidal neurons. The remaining postsynaptic structures were dendritic shafts, many of which had the morphological characteristics of local circuit neurons. The prefrontal injections also labeled associational projections that traveled through the white matter to terminate in other areas of prefrontal cortex. All of the synapses formed by these associational axons were asymmetric, and 91.9% were onto dendritic spines. The similarities in synaptic targets of the prefrontal intrinsic and associational axon terminals suggested that these projections might arise from the same neurons, an interpretation confirmed in dual label, retrograde tracing studies. To determine the specificity of the synaptic targets of these prefrontal connections, two additional comparisons were made. In the posterior parietal cortex (area 7a), 94.2% of the synapses furnished by BDA-labeled intrinsic collaterals of supragranular pyramidal neurons were also with dendritic spines. In contrast, only 75.6% of unlabeled asymmetric synapses in the prefrontal cortex were onto dendritic spines. These comparisons suggest that the axons of supragranular pyramidal neurons in primate association cortices are preferentially directed to specific targets. Finally, after injections of BDA, a small number of retrogradely labeled pyramidal neurons were observed within the anterogradely labeled clusters of intrinsic axon terminals. At the ultrastructural level, synapses between anterogradely labeled axon terminals and retrogradely labeled dendritic spines were identified. These findings suggest that reciprocal, monosynaptic connections may exist between pyramidal neurons located in different stripe-like clusters, providing a potential anatomical substrate for reverberating excitatory circuits within the primate association cortices.