The determination of urinary 3-methoxy-4-hydroxyphenylethylene glycol (HMPG), a major metabolite of epinephrine and norepinephrine by gas-liquid chromatography and electron capture detection is described. A purified extract of HMPG was treated with trifluoroacetic anhydride to form the highly sensitive HMPG-trifluoroacetate derivative. Chromatography was performed on a 6% QF-1-0065 column at 158°. Recovery was found to be 55.4% using [3H]MPG. Two sets of eight identical samples demonstrated a standard deviation from the mean of 6.9% and 5.7%. Thirty-five normal human urine specimens assayed by this procedure gave a mean HMPG excretion of o.86μg/mg creatinine (range 0.25-1.49). Six urine samples from patients with proven pheochromocytoma, and four from patients with proven neuroblastoma were analyzed and gave rise to the anticipated elevation in HMPG excretion. The high sensitivity of this procedure points to the possibility of estimation of plasma HMPG levels.