Intracellular microelectrodes have been used to examine the effects, on excitatory inputs to myenteric nerve cells, of lesions of intrinsic pathways in the myenteric plexus of the guinea-pig small intestine. The lesions consisted of circumferential cuts (myotomies) which severed the external musculature to the depth of the submucosa and thus interrupted pathways in the myenteric plexus. Sufficient time was allowed between creating the lesions and recording from the neurons for the endings of severed neurites to degenerate and this was confirmed histochemically by examining the distribution of varicose fibres with 5-hydroxytryptamine immunoreactivity in myenteric ganglia from which recordings were made. Two types of excitatory input, eliciting fast and slow excitatory post-synaptic potentials, respectively, were demonstrable in response to focal stimulation of nerves in the ganglia from which recordings were made. There were no differences in the proportions of neurons in which fast or slow excitatory synaptic potentials were evoked in unoperated preparations (controls), in islands 1.5-4 mm wide between myotomies, or within 1 mm on the oral or anal sides of myotomies. Possible differences in the amplitudes, durations at half amplitude, and threshold numbers of stimuli for initiation of slow excitatory synaptic potentials were analyzed. The only significant differences were found when data from control and oral areas were pooled and compared with combined data from island and anal areas (this assessed differences that could arise from severing nerve fibres running from oral to anal). The threshold number of pulses for initiation of slow excitatory synaptic potentials in the AH subclass of nerve cells was increased, and their durations were reduced by severing descending axons, but the maximum amplitudes were unchanged. Slow excitatory synaptic potentials of normal amplitude and frequency of occurrence were observed in ganglia in which nerve endings with immunoreactivity for 5-hydroxytryptamine, vasoactive intestinal peptide, somatostatin, enkephalin and gastrin-releasing peptide would have degenerated. It is concluded that none of these substances is essential for the generation of slow excitatory synaptic potentials in myenteric neurons. Descending nerve fibres may make some contribution to the excitatory synaptic potentials evoked in AH cells by close focal stimulation. The results also suggest that many of the cholinergic neurons that contribute to fast excitatory synaptic potentials in S cells project for short distances (less than 1-2 mm) along the intestine and that neither 5-hydroxytryptamine nor the peptides in neurites which degenerate close to lesions (see above) co-exist with acetylcholine in these short neurons.