A specific radioimmunoassay for insulin-like growth factor-binding protein 3 (IGFBP-3), developed against its binding subunit (IGFBP-3 beta), was used to investigate its diagnostic potential for the evaluation of growth disorders. Various factors were found to influence serum IGFBP-3. Most prominent was its considerable age dependence, showing low levels at birth and a peak at puberty. Its dependence on nutrition was obvious from a reduction by 16% after a 3-day fast. Low levels were observed in patients with impaired hepatic function due to biliary atresia, suggesting that the liver may be a major source. In end-stage renal failure, excessively high concentrations were found due to the accumulation of IGFBP-3-related low-molecular-weight forms, suggesting that the kidneys play an important role for clearance. The dependence of serum IGFBP-3 on GH was evident from a significant correlation with total spontaneous nocturnal GH secretion (n = 43; r = 0.62, p less than 0.001). Constant levels over 24 h and a slow response to GH in patients with GH deficiency indicate slow kinetics of variation. Therefore, serum IGFBP-3 appears to reflect the integrated GH secretion over days. In patients with GH deficiency, IGFBP-3 levels were below the 5th percentile of the normal range (133 of 137). In contrast, children with normal-variant short stature (136 of 142) had levels above this limit. Normal IGFBP-3 levels were also found in Turner syndrome and Silver-Russell syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)