An immunocytochemical technique that allows visualization of two antigens in the same neuron was used to verify the possibility that some neocortical pyramidal neurons contain both glutamate (Glu) and substance P (SP) immunoreactivity. The results show that a large fraction of SP-positive pyramidal neurons are also Glu-positive, and indicate that in a small population of cortical neurons a fast excitatory synaptic transmitter and a slow peptidic modulator coexist.