In order to compare the clinical effects of buserelin on central precocious puberty to its excretion in urine, as a parameter of metabolism or compliance, we have studied 52 patients treated either sc or intranasally. In girls with good control, urinary buserelin excretion represented 0.5 ± 0.1% of the daily intranasal dose vs 12.5 ± 2.3% of the daily sc dose. In boys, it represented 0.8 ± 0.2 and 9.9 ± 2.7%, respectively. In the sc treated group, 3 patients (2 girls and 1 boy) with poor control who exhibited excretion levels similar to those with good control were classified as resistant to therapy. Clinical control was poor in 4 intranasally treated girls: 2 had low excretion values suggesting poor compliance or failure of absorption by the nasal mucosa, and 2 appeared resistant to therapy, as urinary excretion levels of buserelin were similar to those of well-controlled patients. In addition, these data suggest that the small amount of buserelin absorbed by the nasal mucosa, as expressed by urinary excretion, is sufficient to desensitize the pituitary gonadotropes without any significant first-pass effect in the systemic circulation. This may explain the clinical effectiveness of the intranasal route for administration of small hormonal peptides acting on the pituitary gland.