Gender affects the GH secretory pattern both in normal subjects and in patients with acromegaly by an uncertain mechanism. Here, we report the influence of gender on the relationship between serum GH and IGF-I levels and the GH response to dynamic tests in patients with acromegaly. Seventy-four patients with untreated acromegaly (M/F 27/47, age range 22-86 yr.) were studied. The serum GH levels did not differ between male and female (6.1 vs. 8.7 ng/ml; p=0.26), while serum IGF-I levels, IGF-I SDS and the IGF-I/GH ratio were lower in female than those in male (679 vs. 769 ng/ml; p<0.02, 7.3 vs. 9.2 SDS; p<0.02 and 79.6 vs. 141.5; p<0.05). When the subjects were divided into two groups: age ≤50 yr, and age >50 yr, serum IGF-I levels and IGF-I/GH ratios were lower in female than those in male in patients ≤50 yrs (650 vs. 1002 ng/ml; p<0.05 and 59.8 vs. 142.9; p<0.05), but not in patients >50 yrs (684 vs. 680 ng/ml; p=0.39 and 98.7 vs. 118.4; p=0.40). The GH responses to OGTT, TRH, octreotide, and bromocriptine tests were similar in male and female. In conclusion, IGF-I/GH ratio was significantly lower in female than that in male particularly in younger patients with acromegaly. These data suggest that gender, presumably sex steroids in female, may partially modulate the relationship between circulating IGF-I and GH levels in patients with acromegaly.