Within- and across-day stability of unconjugated plasma 3-methoxy-4-hydroxyphenethyleneglycol (pMHPG, the major metabolite of norepinephrine) levels were assessed in several subgroups of 47 primarily child and adolescent subjects with Tourette's syndrome (TS). Mean morning pMHPG levels remained stable over a 20-min period from 8:30 to 8:50 AM at 3.5 +/- 0.8 ng/ml. However, the mean intraindividual fluctuation in pMHPG levels over 20 min was +/- 12%. Mean pMHPG levels remained stable in the morning from 8:00-8:30 AM to noon. However, an 11% decrease (p less than 0.01) in mean pMHPG levels was observed in the afternoon between noon and 3:00-4:00 PM. Monitored on consecutive days, mean morning pMHPG levels fell 12% (p less than 0.002). The afternoon and across-day falls in pMHPG levels observed in this study of primarily children and adolescents with TS have not been observed in studies of adult control subjects. The results suggest that the design of research protocols involving children and adolescents that use pMHPG should take into consideration the effects of time, both within- and across-day, in pMHPG levels.