Conditioning for bone marrow transplantation (BMT) by total body irradiation frequently causes growth failure. The contribution of growth hormone (GH) deficiency to this failure was assessed in 38 patients given three types of body irradiation: group 1 (n=18) was given 12 Gy total body irradiation as six fractions, group 2 (n=14) 10 Gy (one dose) total body irradiation, and group 3 (n=6) 6 Gy (one dose) thoracoabdominal irradiation, which did not involve the hypothalamic-pituitary area. At the first evaluation, 2.9±0.2 (SE) years after BMT, the values for the plasma insulin-like growth factor I (IGF-I) and its GH-dependent binding protein (IGFBP-3) were similar in groups 1 and 2 but significantly greater in group 3 (p<0.02 for IGF-I and 0.01 for IGFBP-3). These values were similar in those patients in groups 1 and 2 who had low GH peaks after stimulation (12 patients: IGF-I, 0.8±0.2 U/ml; IGFBP-3, 1.6±0.2 mg/L) and in those with normal GH peaks (20 patients: 1±0.1 U/ml and 1.8±0.1 mg/L). The decrease in height 2 years after BMT was significantly (p<0.01) greater in group 2 than in groups 1 and 3, but 5 years after BMT it was similar in groups 1 and 2 (0.9±0.2 and 1.4±0.3 SD), significantly (p<0.05) greater in group 2 than in group 3 (0.7±0.2 SD). The individual height changes between BMT and the last clinical evaluation before GH therapy were not correlated with the age at BMT, GH peak after stimulation, plasma IGF-I concentration, or IGFBP-3 concentration. Seven patients with GH deficiency were given GH therapy; their growth rate became normal for age (−2.1±0.9 SDS before and −0.2±0.4 SDS for the first year; not significant) without any catch-up growth. We conclude that plasma IGF-I and IGFBP-3 values are of no diagnostic value for GH deficiency after TBI. Their normal or high levels, despite low GH peaks, suggest that bone irradiation induces lesions causing resistance to IGF-I.