The distribution and synaptic connections of dopamine axons were studied by light and electron microscopy in human cerebral cortex. For this purpose, dopamine immunoreactivity was characterized in apparently normal anteriolateral temporal cortex, which was removed to gain access to the medial temporal lobe during tumor excision or treatment of epilepsy. Nissl sections showed this to be granular neocortex. Dopamine fibers were distributed throughout this cortex, although there were relatively more fibers in layers I-II and in layers V-VIa, compared to layers III-IV and VIb, resulting in a bilaminar pattern of labeling. In all layers, fibers were seen to form numerous varicosities, and to vary in size from thick to very fine. Fibers were relatively straight, sparsely branched and were oriented in various planes within the cortex. However, in layer I, they often ran parallel to the pial surface. In order to analyze the functional interactions of dopamine fibers, individual cortical layers were surveyed for dopamine synapses. These were usually symmetrical (Gray's type II), although 13% of them were asymmetrical. Approximately 60% of dopamine synapses were made with dendritic spines, and 40% with dendritic shafts, and this ratio was similar in all layers. On both spines and shafts, it was common to see dopamine synapses closely apposed to an unlabeled asymmetric input, suggesting a dopamine modulation of excitatory input. Some postsynaptic dendritic shafts had features of pyramidal cells, including formation of spines. Since pyramidal cells are the major type of cortical spiny neuron, they probably represent the main target of dopamine synapses in this cortex. There were also dopamine profiles apposed to membrane densities on unlabeled axon terminals, suggesting another type of synaptic interaction. These findings provide the first documentation of dopamine synapses in the human cortex, and show that they form classical synaptic junctions. The location of these synapses on spines and distal dendrites, and their proximity to asymmetric synapses, suggest a modulatory role on excitatory input to pyramidal cells.