Using immunocytochemical methods, the proportion of calcitonin gene-related peptide immunoreactive perikarya was determined in dorsal root ganglia L4–L6 in four control rats and in ten rats with a unilateral inflammation in the ankle region of the left hindlimb. The inflammation was induced by subdermal injection of Freund's complete adjuvant at the ankle. Swelling and cellular infiltration of the ankle region developed within 2 days, and were stable and restricted to the injected ankle for the duration of the 3-week study. In control rats ∼24% of 20 419 perikarya showed calcitonin gene-related peptide (CGRP)-like immunoreactivity. In rats with unilateral inflammation the proportion of CGRP-positive neurons was increased on the inflamed side to ∼32% of 11 454 cells at day 2 (P < 0.001 with respect to ganglia in normal rats) and ∼29% of 10 739 perikarya at day 20 post inoculation (P < 0.01). By contrast, no significant changes were found between ganglia in the non-injected side (∼25% at day 2 and ∼24% at day 20). These results demonstrate that peripheral inflammation is associated with an increase in the proportion of neurons in the dorsal root ganglia that synthetize CGRP. This up-regulation is already present at an early stage of inflammation but also at later stages, suggesting that the increased synthesis of CGRP is an important neurobiological reaction associated with the acute and chronic phases of inflammation.