The effects of glucocorticoids on cancellous bone remodeling and structure are well documented but there are no reported histomorphometric studies in human cortical bone in glucocorticoid-treated patients. We have performed a histomorphometric analysis of iliac crest cortical bone in 14 patients treated with glucocorticoids, 9 females and 5 males, aged 18 to 48 years (34.1 ± 7 years) (mean ± standard deviation [SD]). The underlying disease was cystic fibrosis in 8 patients; asthma 3; and nephrotic syndrome; Crohn disease and inflammatory pseudotumor of the liver in one patient each. Results were compared with an age-matched control group of 10 premenopausal women and 4 men aged 22 to 38 years (30.1 ± 4.8 years) who were not, howerver matched for underlying disease. Cortical bone indices were assessed by image analysis. Cortical width and area were similar in the two groups. However, cortical porosity, Haversian canal number, and density were higher in patients treated with glucocorticoids compared with controls (8.4 ± 8.9% vs. 5.1 ± 3.9%; P = 0.03) (45.9 ± 23.2 vs. 31.9 ± 24.4; P =0.003) (13.7 ± 9.4 vs. 6.7 ± 3.3/mm2; P = 0.00005). Haversian canal area did not differ significantly between groups. The mean wall width of the osteons, bone formation rate (μm2/μm/day) and mineral apposition rate (μm/day) were lower in treated patients compared to controls (48.8 ± 7.1 μm vs. 59.8 ± 12.9 μm; P = 0.01) (0.056 ± 0.040 vs. 0.095 ± 0.058; P = 0.05) and (0.59 ± 0.12 vs. 0.75 ± 0.11; P = 0.002). The proportion of canals with an eroded surface was lower in the treated compared with the control group, although this difference was not statistically significant. These results demonstrate that cortical porosity is increased in patients treated with long-term glucocorticoid therapy, due mainly to an increase in the number rather than size of Haversian canals. This may be because of increased bone resorption during the early stages of glucocorticoid therapy, in combination with long-term impairment of bone formation. Effects of the underlying disease on bone remodeling may also contributed to these changes and could not be excluded in the present study; since control subjects were not matched in terms of disease status.