Cerebrospinal fluid (CSF) levels of substance P like immunoreactivity (SPLI) were determined in 11 patients with painful osteoarthritis in hip or knee, 9 patients with rhizopatic pain from a herniated lumbar disc, and in 9 healthy volunteers without pain. The patients with osteoarthritis had increased levels of SPLI in CSF (p < 0.001) compared to the controls. A positive correlation was also seen between the CSF SPLI and the degree of pain. At a second lumbar puncture 5 months after operation, SPLI had decreased, but was still significantly higher than in the controls. No difference in CSF SPLI was seen in the patients with herniated lumbar disc compared to the controls, neither before treatment, nor at follow up CSF postoperatively. The results suggest that nociceptive joint pain is consistent with increased SPLI in CSF. Differences in SPLI in CSF may be useful to differentiate pain from various origin, and may also increase our understanding of different pain mechanisms.