This investigation was to our knowledge the first to use the microdialysis technique to study concentrations of substances in a human tendon. In four patients (mean age 40.7 years) with a painful nodule in the Achilles tendon (chronic Achilles tendinosis) and in five controls (mean age 37.2 years) with normal Achilles tendons (confirmed by ultrasonography) the local concentrations of glutamate and prostaglandin E2 were measured under resting conditions. A standard microdialysis catheter was inserted into the Achilles tendon under local anesthesia. Sampling was performed every 15 min over a 4-h period. The results showed significantly higher concentrations of glutamate in tendons with tendinosis than in normal tendons (196 +/- 59 vs. 48 +/- 27 mumol/l, P < 0.05), and there were no significant changes in glutamate concentration over the period of investigation. There were no significant differences in the mean concentrations of prostaglandin E2 (83 +/- 22 vs. 54 +/- 24 pg/ml) between tendons with tendinosis and normal tendons. In conclusion, in situ microdialysis appears a useful method to study certain metabolic events in tendon tissue. The higher concentrations of the excitatory neurotransmitter glutamate in Achilles tendons with a painful nodule may possibly be involved in the pain mechanism in this chronic condition. Furthermore, there were no signs of inflammation in the tendons with painful nodules, as indicated by the normal prostaglandin E2 levels.