Synthetic thyrotropin releasing hormone (TRH) was administered intravenously to normal human subjects to define the normal range of serum thyrotropin (TSH) response to TRH and some of the variables that affect this response. The maximum increase in serum TSH (maximum ΔTSH) following TRH was employed as the index of response. These were the results: 1) The maximum ΔTSH increased linearly when the TRH dose was increased from 6.25 to 400 μg. Since 800 μg produced no greater response than 400 μg, 400 μg is recommended as the standard test dose for evaluating TSH secretion. 2) Consistency of TSH response was evaluated by administration of the same dose (400 μg) of TRH to each of five subjects on four different occasions. The coefficients of variation of the maximum ΔTSH's in each subject ranged from 11–22% in four subjects and was 40% in the fifth. 3) TSH responsiveness to TRH was not significantly affected by sex. maximum ΔTSH in 20–39 year-old females was 16.8 ± 1.6 μU/ml (mean ± sem), and that in height- and weight-matched, 20–39 year-old males was 14.3 ± 1.7 μU/ml. 4) TSH responsiveness to TRH diminished significantly with increasing age, from a maximum ΔTSH of 14.3 ± 1.7 μU/ml in 20–39 year-old males, to 9.1 ± 2.1 μU/ml in 40–59 year-old males, to 6.1 ± 1.2 μU/ml in 60–79 year-old males. These groups also were matched closely for height and weight. The implication for the clinical use of TRH is that age-specific ranges of normal must be used to avoid diagnostic error.