We have attempted to identify which subpopulations of rat sensory neurons possess functional neurotransmitter receptors which elevate the free concentration of intracellular calcium. Subpopulations of sensory neurons were identified using three accepted criteria: (i) the distribution and proportion of neurons with differing somatic diameters; (ii) the expression of substance P-like immunoreactivity; and (iii) the responsiveness of each neuron to capsaicin. The total neuronal population was primarily grouped into three classes according to somatic diameter and defined as small- (< 17 microns), intermediate- (17-25 microns) and large- (> 25 microns) sized neurons. It was not possible to distinguish between small and intermediate-sized neurons since a similar percentage of each class expressed substance P-like immunoreactivity or sensitivity to capsaicin. Large-sized neurons did not possess these characteristics and, therefore, represented a distinct neuronal population. In single, intact neurons of differing diameter, the ability of a variety of receptor agonists to elevate the free concentration of intracellular calcium was determined using the calcium-sensitive indicator, Fura-2. Local application of capsaicin, adenosine, bradykinin, ATP and substance P elevated the resting level of the free concentration of intracellular calcium in small and intermediate-sized neurons. The large-sized neurons were unresponsive to these receptor agonists with the exception of ATP. The response to ATP was relatively transient in nature and did not differ between neurons of differing somatic diameter.(ABSTRACT TRUNCATED AT 250 WORDS)