1. Central nervous system (CNS) side effects are observed during treatment with all nonsteroidal anti-inflammatory drugs (NSAIDs) but their effects are more common during treatment with indomethacin. 2. The aim of the study was to elucidate the mechanism of the CNS related side effects of indomethacin. Two groups were obtained, one with (n = 11), and one without (n = 7), CNS symptoms. Cerebral blood flow was measured in these groups with Doppler equipment, indomethacin levels with h.p.l.c. and CNS symptoms graded on a VAS scale. 3. Blood flow was reduced by 18-30% and was most marked 60 min after dose and did not differ between the two groups. The maximum CNS effect coincided with indomethacin peak levels 60-70 min after dose. These results could implicate that CNS symptoms may be related to indomethacin levels in sensitive patients.