The influence of hGH treatment on spontaneous chromosome aberrations and chromosome fragility was tested in 23 naive patients aged 4 to 16 years. The breaking action of ionizing radiation was used as an indicator of chromosome fragility. 17 patients had growth hormone deficiency, 1 Turner syndrome, and 5 neurosecretory growth hormone dysfunction. Blood samples were taken at baseline and following 6 months of hGH treatment (0.3 mg/Kg/week). Lymphocyte cultures and cytogenetic preparations were established using standard cytogenetic techniques. Half of the cultures were irradiated with 3 Gy of gamma rays. All mitotic preparations were coded to ensure “blind” enumeration of aberrations. A one-way ANOVA was performed on log transformed data for analysis of aberrations per cell. There were no significant differences between pre-treatment (9,500 cells) and post-treatment (8,000 cells) cells for spontaneous chromosome-type aberrations (mean ± SEM) 4.2 × 10-3 ± 1.2 × 10-3 vs 7.9 × 10-3 ± 2.9 × 10-3 (p=0.08); for chromatid-type aberrations 9.2 × 10-3 ± 2.8 × 10-3 vs 1.1× 10-2 ± 4.0 × 10-3 (p=0.42); and for total aberrations (chromosome + chromatid) 1.3 × 10-2 ± 3.0× 10-3 vs 1.9 × 10-2 ± 7.0 × 10-3 (p=0.10). There were also no significant differences for radiation-induced aberrations (4,550 pretreatment cells and 4,850 post-treatment cells) for chromosome aberrations 1.12 ± 3.0 × 10-2 vs 1.05 ± 5.0 × 10-2 (p=0.18); for chromatid aberrations 2.6 × 10-2 ± 5.0 × 10-3 vs 2.0× 10-2 ± 3.0 × 10-3 (p=0.60); and for total aberrations 1.15 ± 3.0 × 10-2 vs 1.07 ± 5.0 × 10-2 (p=0.17). However, when the data were analyzed on a per chromosome basis (i.e. number of aberrant chromosomes ÷ total number of chromosomes scored) with binomial probability being applied to the raw data, small but significant differences were seen. Total spontaneous aberrations per cell (mean with 95% confidence limits) were: pre-treatment 2.65 × 10-4 (2.18 × 10-4 to 3.13 × 10-4) vs post-treatment 3.42 × 10-4 (2.83 × 10-4 to 4.02× 10-4) p<0.05), and for total radiation-induced aberrations 2.51 × 10-2 (2.44 × 10-2 to 2.57 × 10-2) vs 2.40 × 10-2 (2.34 × 10-2 to 2.47× 10-2) (p<0.05). This analysis suggests that 6 months of hGH treatment may lead to a significant increase in spontaneous chromosome aberrations and significant decrease in chromosome fragility. The disparity between the chromosome aberration and fragility data is unexplained and requires further investigation.