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Notes: Using mono - and bilateral tarsal arthritic models in the rat, we have previously shown increases in the expression of mRNAs encoding substance P and calcitonin gene-related peptide (CGRP) in primary sensory neurons innervating inflamed joints. Dorsal root ganglion (DRG) neuropeptide content in rats is altered by glucocorticoids, and since glucocorticoids regulate the expression of preprotachykinin (PPT) gene, the substance P precursor in other tissues, these effects may be mediated at the level of transcription. Indeed adrenalectomy potentiates disease in polyarthritis although the relationship to joint disease itself is unclear. Secretion of corticosterone in both mono -and bilaterally inflamed rats showed a loss of the normal diurnal nadir with no elevation of evening values. However, there were no changes in glucocorticoid target organs (adrenal gland, thymus and spleen) suggesting the stress was intermittent. Adrenalectomy in mono - and bilaterally inflamed rats did not significantly alter either the severity of inflammation or its spread. Bilaterally inflamed animals did, however, show reduced weight gain. Adrenalectomy had no effect on the induction of PPT and CGRP mRNA expression in innervating DRG neurons in monoarthritis (14 days after adjuvant injection), the unilateral increase in both PPT and CGRP mRNA expression in ADX animals being similar to SHAM arthritic rats. (PPT: ADX 140 ± 13 left; 99 ± 6 right % control; SHAM 160 ± 22 left, 100 ± 5 right % control. CGRP: ADX 177 ± 6 left, 97 ± 3 right % control; SHAM 147 ± 21 left, 100 ± 5 right % control). In bilaterally arthritic rats adrenalectomy potentiated the increase in CGRP mRNA expression (SHAM 168 ± 6% left, 271 ± 23% right; ADX 217 ± 38% left, 193 ± 4% right; control 100 ± 5%) but significantly attenuated the contralateral (right) increase in PPT mRNA expression seen in sham-operated rats (SHAM 136 ± 21% left; 140 ± 11% right; ADX 145 ± 28% left, 86 ± 15% right; control 100 ± 5%). Inflammation-associated changes in somatostatin mRNA expression were similar in sham-operated and adrenalectomized rats. We conclude, therefore, that whilst adrenalectomy exerts subtle effects on the expression of PPT and CGRP mRNAs in DRG neurons in bilateral arthritis, the presence or absence of high circulating endogenous corticosteroids in these animals, with limited arthritis, do not modulate the arthritic process.