The presence of tele-methylhistamine (t-MH), the metabolite of histamine in rat brain, and its relationship to putative histaminergic transmission have been the subjects of recent work. We modified the GCMS method of Hough et al. (1979) to enhance both sensitivity and reproducibility. The substitution of KOH for NaOH to extract t-MH considerably improved the recovery. Evaporation of the extract in 0.2 N HCl, as used in the earlier method, reduced the formation of heptafluorobutyryl derivative; substitution with 0.01 N HCl more than doubled the recovery of the derivative. The derivatization procedure itself was changed, the new method exhibiting significantly improved reproducibility. Standard curve of t-MH obtained at different times after derivatization were indistinguishable. The modified method is capable of measuring less than 1 pmole of t-MH. The t-MH content found in nine rat brain regions agree with previously reported values.