Endogenous opioids are thought to participate in the regulation of growth hormone (GH) release through the mediation of growth hormone releasing hormone (GHRH). This study was intended to investigate whether the endogenous opioid beta-endorphin could modulate the GH response to GHRH and if this hypothesis could be demonstrated in children with familial short stature with or without constitutional growth delay. Seventeen children (6 female and 11 male) with stature below the fifth percentile were studied to rule out disorders in growth hormone dynamics. All had normal growth velocities, had appropriate predicted heights for their families and had normal GH levels on standard testing. Eight were prepubertal and 9 were Tanner II. All were given 0.1 mcgm/kg (1-44)hpGHRH-NH2 IV. Blood for growth hormone was obtained at 0, 15, 30, 45, 60, 90 and 120 minutes. Blood for beta-endorphin and cortisol was obtained at 0 and 60 minutes. The basal beta-endorphin level significantly correlated with the peak GH level (r = 0.868, p less than 0.05) in the prepubertal group only. In the same group of children, the degree of the negative feedback on the beta-endorphin level correlated significantly with the rise in GH level (r = 0.912, p less than 0.01). However, there was no correlation between the basal beta-endorphin and the peak GH level nor between the rise in GH level and the change in beta-endorphin in the pubertal children. These data are compatible with the hypothesis that beta-endorphin levels affect the GH response to GHRH in prepubertal children, but have no discernible effect on the GH response to GHRH in pubertal children.