BACKGROUND AND OBJECTIVE: Inhibins are peptides, mainly of gonadal origin, that suppress FSH production. Dimeric forms of inhibin (A and B) have been proposed as peripheral markers of Sertoli and granulosa cell function. The aim of this study was to establish the relationship between circulating dimeric and monomeric inhibins, and gonadotrophins and sex steroids, in normal boys and girls from birth to puberty. SUBJECTS: One hundred and forty-six normal children (females: 57; males: 89) were studied. MEASUREMENTS: Serum LH and FSH were measured by an immunofluorometric assay. Serum oestradiol and testosterone were measured by radioimmunoassay. Serum inhibin A and B, and Pro-alphaC, were measured by specific two-site enzyme-linked immunosorbent assays. RESULTS: In boys from birth to 6 months of age, the mean serum inhibin B concentration was as high (477 +/- 53.7 ng/l) as that found at puberty (400 +/- 70.2 ng/l). After the first year, inhibin B gradually decreased to reach its lowest concentration (153 +/- 23.6 ng/l) at age 4-6 years. At approximately age 10, it rose progressively to reach pubertal concentrations. Pro-alphaC showed a similar pattern but at lower concentrations. Inhibin A was not detected at any age. In girls from birth to 6 months, inhibin B levels (83.0 +/- 18.3 ng/l) were approximately 50% lower than those found at puberty (181 +/- 25.7 ng/l). After 6 months of age, these levels dropped (17.5 +/- 1.6 ng/l) and remained low until the prepubertal years. Thereafter, they increased to pubertal concentrations. The serum inhibin A concentration after birth (29.9 +/- 8.7 ng/l) was similar to that found at puberty (18.3 +/- 5.7 ng/l); after 6 months, it fell to undetectable levels until the prepubertal years. CONCLUSION: The sex difference in serum levels of gonadotrophins is associated with sex differences in the levels and proportions of circulating dimeric and monomeric inhibins.