A decreased growth hormone response to various secretagogues has been described in Turner's syndrome, but the mechanisms responsible for this decrease are unknown. Seventeen prepubertal girls with Turner's syndrome (age 6.4 to 15.7 years; height -0.2 to -5.4 SD, bone age -3.7 to -0.3 SD; weight 93 to 169% of ideal body weight) underwent a stimulation test with GHRH (0.5 micrograms/kg). Plasma GH and prolactin were measured by radioimmunoassay from -30 to +120 min and insulin-like growth factor-I at time 0. These values were compared with those observed in lean children with constitutional short stature. Peak plasma GH after GHRH was 17.0 +/- 3.6 micrograms/l (mean +/- SEM), significantly lower (p less than 0.001) than in the short lean children (39.2 +/- 5.1 micrograms/l). In Turner's syndrome patients, the peak GH value was negatively correlated with the percentage of ideal body weight (r = -0.58, p less than 0.02) and of body fat (r = -0.59, p less than 0.02). Plasma prolactin levels in Turner's syndrome did not rise after GHRH and showed a normal circadian variation, from 8.0 +/- 1.0 micrograms/l at 08.30 h to 5.0 +/- 0.7 micrograms/l at 11.00 h (mean +/- SEM). Mean (+/- SEM) baseline plasma insulin-like growth factor-I concentrations was 0.88 +/- 0.14 kU/l, higher than in the short lean children (0.49 +/- 0.08 kU/l, p less than 0.05). We conclude that the decreased GH response to GHRH of girls with Turner's syndrome is related, at least in part, to their excess body weight and fat and is associated with higher IGF-I levels than in short lean children.