The response of hematopoietic progenitors to the growth promoting effects of hGH and IGF-I has been documented. In this study, the effects of recombinant hGH and IGF-I on the growth of circulating erythroid burst forming cells (BFU-E) from growth-IGF-I retarded children with insufficient growth hormone secretion (IGHS) were evaluated and compared with values obtained from either children with short stature and normal growth hormone levels (SNGH) or normal donors. Both recombinant hGH and IGF-I had significantly greater stimulatory effects on the growth of BFU-E from the IGHS compared with the SNGH and with the normally growing children. At its optimal concentration of 200 μg/L, recombinant hGH had a stimulatory effect on the growth of BFU-E from 11 IGHS children yielding a mean ± SD value of 2.0 ± 0.3-fold above the unstimulated controls compared with 1.45 ± 0.16-fold and 1.36 ± 0.04-fold stimulation of BFU-E from six SNGH and five normal donors, respectively. Similarly, IGF-I, at its optimal concentration of 0.065 nmol/L (0.5 ng/mL), stimulated IGHS-derived BFU-E growth 1.67 ± 0.25-fold above unstimulated controls, compared with 1.28 ± 0.17-fold and 1.3 ± 0.1-fold stimulation of BFU-E from SNGH and from normal donors, respectively. The hGH- and IGF-I-induced stimulatory effects could be neutralized by their respective specific MAb. This significantly increased reactivity of erythroid progenitors from growth-retarded IGHS children to the erythropoietic effects of hGH and IGF-I may be the result of increased availability of cell surface receptors to these hematopoietic “synergistic” factors, secondary to their ambient decreased circulating concentrationsin vivo.In vitrostudies of peripheral blood BFU-E responsiveness to hGH and to IGF-I may be useful in implicating these peptides in growth retardation and possibly in predictingin vivoresponse to them. (Pediatr Res 32: 282–285, 1992)