Afferent inhibition in several distinct types of cuneate neurons was studied using controlled natural stimuli in 35 lightly anesthetized cats. Mechanoreceptive cuneate neurons were recorded extracellularly with microelectrodes from the middle and caudal divisions of the main nucleus. They were classified into several modality subtypes based on their response to adequate mechanical stimuli. Emphasis was laid on the neurons which had their receptive fields (RFs) in the forepaw. Afferent inhibition was induced by conditioning tactile stimuli in 31 out of 168 neurons (18%) tested. There were particular combinations between the neuron types inhibited and conditioning stimulus modalities. Dynamic stimuli such as high frequency vibration and hair movement by air-jet stimuli applied to areas beyond the excitatory RFs induced inhibition on touch (T), hair (H) and slowly adapting pad (SA) units predominantly in the paw region. In contrast, steady pressure stimulation on the skin adjacent to the excitatory RFs induced inhibition in exclusively slowly adapting neurons receiving afferent inputs from hairy skin such as touch (T), joint (J) and subcutaneous (Deep) units in the paw, elbow and shoulder regions. Most of the inhibitory RFs were organized laterally or eccentrically rather than concentrically around the excitatory RF. Two J units were found to be inhibited by steady pressure applied to the shoulder region of the contralateral forelimb. Functional significance of the intramodality and cross modality inhibition of cuneate neurons is discussed.