The cell body size (cross-sectional area) of S100-immunoreactive (-ir) primary neurons was measured in the trigeminal (TG) and lumbar dorsal root ganglia (DRG). About a half of neurons exhibited S100-immunoreactivity (-ir) in the DRG (44.0%) and TG (59.0%). DRG neurons with cell bodies > 1200 microm2 mostly exhibited S100-ir (96.5%), whereas S100-ir DRG neurons < 600 microm2 were rare (8.0%). 36.6% of DRG neurons in the cell size range 600-1200 microm2 showed the ir. TG neurons > 800 microm2 mostly exhibited S100-ir (93.1%), whereas those < 400 microm2 were devoid of it (positive cells 10.5%). 58.3% of TG cells in the range 400-800 microm2 contained S100-ir. Double-immunofluorescence method revealed the co-expression of S100 and other calcium-binding proteins. Parvalbumin-ir neurons mostly exhibited S100-ir in the DRG (97.4%) and TG (97.0%). The co-expression of S100 and calbindin D-28k was very rare in the DRG, because the DRG contained few calbindin D-28k-ir neurons. Unlike in the DRG, numerous neurons co-expressed S100- and calbindin D-28k-ir in the TG. Most calbindin D-28k-ir TG neurons were also immunoreactive for S100 (90.7%). Sub-populations of calretinin (CR)-ir neurons co-expressed S100-ir in both the DRG (68%) and TG (50.0%). Virtually all CR-ir neurons > 1400 microm2 co-expressed S100-ir in the DRG (100%) and TG (95.9%). CR-ir neurons < 800 microm2 were rarely exhibited S100-ir (DRG 18.0%, TG 21.9%). 71.3 and 60.5% of CR-ir neurons in the range 800-1400 microm2 co-expressed S100-ir in the DRG and TG, respectively. The present study indicates that S100 is closely correlated to the primary neuronal cell size in the DRG and TG.