To investigate whether or not a cholinergic pathway is involved in the paradoxical response of GH to TRH in constitutionally tall children, we studied 8 healthy prepubertal children aged 4 2/12-7 10/12 yr, whose heights were over the 95th percentile of the NCHS tables. We defined as "paradoxical" a GH increment greater than 5 ng/ml in response to TRH. Five out of 8 children showed a paradoxical response of GH to TRH (mean GH peak after TRH of 10.7 +/- 1.1 ng/ml). Pretreatment with atropine (0.01 mg/kg IM 30 min prior to the TRH administration) abolished the TRH induced GH rise (peak GH after TRH of 1.5 +/- 1.0 ng/ml, p less than 0.01) but did not modify the TSH response (peak TSH after TRH: basal conditions 8.7 +/- 0.8 microU/ml, post atropine: 9.5 +/- 1.4 microU/ml, p greater than 0.05). Our results demonstrate that a cholinergic pathway is involved in the paradoxical response of GH to TRH in constitutionally tall children.