In a study of 11 patients with typical headache following diagnostic lumbar puncture the effect of peroral treatment with theophylline (Euphyllin retard) was compared with that of placebo. When the headache was provoked by orthostatic strain, the six patients in the verum group showed significantly less pain (mean pain score: 16 +/- 3.91) than the five patients in the placebo group (mean pain score: 28 +/- 4.73). This beneficial effect of theophylline on post-puncture headache was subsequently confirmed by open observations of ten additional patients. In view of the small sample size our results should be considered preliminary. Nevertheless, they suggest that additional trials on the benefit of methylxanthines in the treatment of post-puncture headache are called for.