The efficacy of tizanidine in chronic tension-type headache was compared with placebo in a randomized, double-blind and cross-over study in 37 women aged 20 to 59 years with a history of headache for 7 months to 30 years (median 5 years). The treatment periods were 6 weeks with an intervening 2 week wash-out period. The treatment was started with 6 mg/ day divided into three doses, and the daily dose could be increased to 18 rag/day depending on the treatment response. The effect of the treatment was measured by visual analogue scale, verbal rating scale, number of days free of headache, number of analgesics needed, and the dose of trial medication needed. In all these measurements, tizanidine was statistically significantly more effective than placebo. The pre-trial Beck Depression Inventory score did not predict the response to treatment, neither did the level of electromyographic activity of the trapezius muscle. Side-effects, drowsiness and dry mouth were significantly more common during tizanidine treatment but they were usually mild. The results of the present trial suggest that tizanidine is effective in the treatment of chronic tension-type headache in women.