In order to obtain a clinically valuable differentiation of central hypogonadism (CH), 18 male patients, including 13 with permanent gonadotropin deficiency (GD), age 14.3-41 yrs, bone age 8.5-19 yrs, and 5 with constitutional delay (CD) of puberty (age 15.3-20, bone age 12.5-15 yrs) were studied. Among the GD patients, there were 4 with anosmia (Kallmann's syndrome, KS), 6 with idiopathic hypopituitarism (HP) and 3 with isolated hypogonadotropic hypogonadism (HH). The spontaneous nocturnal plasma profile of LH and FSH was compared with that during pulsatile LHRH infusion (5 micrograms iv every 90 min) by a portable micropump (Zyklomat) for 36 hrs. The pituitary-gonadal response was evaluated by calculating the LH and FSH slopes during pulsatile LHRH and by comparing plasma testosterone (T) before and after. While spontaneous nocturnal FSH pulses were absent in all patients, between 1 and 4 significant LH pulses were seen in all CD but in none of the GD patients. In all patients, mean FSH was significantly higher during pulsatile LHRH than during sleep. During pulsatile LHRH administration, significantly increasing FSH responses were seen in all KS and HP patients, but in only 2 of the 5 CD and in none of the 3 HH patients. In all CD boys (mean testis vol, 8.6 ml), T rose markedly during pulsatile LHRH (mean, from 168 to 414 ng/dl), whereas in all GD patients (mean testis vol, 2 ml) it did not (19 vs 27 ng/dl). CONCLUSIONS Pulsatile LHRH for 36 hrs differentiates CD and GD far more exact than was previously possible.(ABSTRACT TRUNCATED AT 250 WORDS)