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Sex hormones have a significant impact on ventilation in mammals. The effects of menstrual cycle, pregnancy, testosterone, estradiol and progesterone on resting ventilation have been well documented. The noradrenergic neurons of locus coeruleus (LC) contain estrogen and androgen receptors and have been reported to regulate the CO2-drive to breathe. We therefore evaluated the role played by sex hormones in the activation of LC noradrenergic neurones in response to CO2 in male rats. We assessed neuronal activity by c-Fos immunoreactivity in gonad-intact (INT) rats and orchidectomized rats treated with oil (ORX), testosterone (ORX+T), or estradiol (ORX + E2). Hypercapnia (7% CO2, 21% O2 and N2 for balance) or normocapnia (control animals) was administered for 2 hrs. The number of c-Fos/tyrosine hydroxylase (TH)-immunoreactive (ir) neurons was counted bilaterally in the LC (c-Fos/TH-ir neurons per section). The results showed that the number of c-Fos/TH-ir neurons in the LC was significantly increased by hypercapnia in INT (9.7 ± 5.7), ORX (7.6 ± 8.9), ORX + E2 (11.3 ± 9.9) and ORX + T (8.1 ± 7.2) male rats compared to normocapnia (3.9 ± 2.4; 2.3 ± 1.4; 2.1 ± 1; 4 ± 4.1, respectively). However, there was no significant effect of hormonal treatments on the response of LC to hypercapnia. These findings suggest that sex hormones seem to play no role in the LC response to hypercapnia in male rats. [ABSTRACT FROM AUTHOR]