1. Responses of thalamocortical projection neurons and suspected cortical interneurons (SINs) to very brief peripheral stimuli were examined within the vibrissae, the sinus hair, the lip, and the chin representations of ventroposterior medial thalamus (VPM) and primary somatosensory cortex (S1). VPM thalamocortical neurons (N = 40) were identified by their antidromic activation after electrical stimulation of S1. SINs were identified by a high-frequency (> 600 Hz) burst of three or more spikes elicited by suprathreshold stimulation of one or more afferent pathways. SINs also had spikes of very short duration. 2. Previous work has shown that electrical stimulation of VPM elicits a very early and powerful synaptic response in many S1 SINs. Three experimental strategies were employed to test the hypothesis that such responses reflect a monosynaptic VPM input onto SINs and to examine the effects of such input. 1) After a brief peripheral stimulus, the arrival times of VPM thalamocortical impulses in S1 were determined and compared with the initial response times of S1 SINs. 2) Shift-corrected cross-correlograms (CCGs) were constructed from the spike trains of pairs of VPM neurons and SINs that were in precise topographic alignment. 3) Inferences of connectivity based on such CCGs were supported by applying very low-intensity (1-10 microA) microstimulation pulses to the recording microelectrode in VPM and observing evoked responses in the cortical SIN. 3. VPM thalamocortical neurons responded to a brief air puff stimulus at a median latency of 5.05 ms, and the estimated arrival time of the VPM impulses at S1 had a median value of 5.97 ms. This estimate was obtained by adding the antidromic latency of each VPM neuron to the latency of the peripheral stimulus and was supported by similar values obtained from three VPM thalamocortical axons recorded near their termination site within S1. SINs of S1 were among the first cortical neurons to respond to the peripheral stimulus, responding to the air puff at a median latency of 6.6 ms (range 5.7-13.0 ms). The latency of SINs to the peripheral stimulus was strongly related to the latency to gross electrical stimulation of VPM (median value 1.52 ms, r2 = +0.44, P < 0.0001). Many SINs (23 of 34) showed significant shift-corrected CCGs with VPM neurons that were in precise topographic alignment. Most significant CCGs revealed a very brief increase in SIN spike probability (half-amplitude response of approximately 1 ms) that reached a peak value at intervals of 1.4-2.0 ms after the VPM spike.(ABSTRACT TRUNCATED AT 400 WORDS)