To evaluate the effect of occupational exposure to manganese (Mn) on serum prolactin (PRL) and the interrelationship among other hypophyseal-pituitary hormones, a cross-sectional study was conducted on 251 welders and 100 age-matched, office workers. We analyzed serum PRL, dopamine (DA), thyroid stimulating hormone releasing hormone (TRH), follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (TST) and measured current airborne Mn concentration in the welders. Cumulative exposure index (CEI) of airborne Mn was calculated. CEI and the present Mn level of the welders were 1.4+/-1.1mg/m3 year (range: 0.0-4.9) and 0.4+/-3.84 mg/m3 (range: 0.0-3.8), respectively. TRH, FSH and LH were higher in welders (5.08 pg/ml, 7.40 and 4.91 mIU/ml, respectively) than in office workers (3.91 pg/ml, 6.15 and 4.00 mIU/ml, respectively) (p<0.05). DA was decreased and TRH was increased significantly with increasing CEI. DA increased up to CEI 2.0mg/m3 year or mean Mn level up to 0.2mg/m3, then decreased. PRL showed increasing tendency above the CEI and mean Mn level at which DA started to decrease. PRL was positively associated with DA in the office workers. However, such a normal feedback control of DA on PRL was not observed in the welders. Structural equation model (SEM) analysis showed that CEI was positively related to TRH and negatively related to DA. TRH increased PRL. PRL increased LH and perhaps FSH, and on the other hand, decreased TST. These results showed that Mn suppresses the inhibitory feedback control of DA on the hypophyseal-pituitary axis. In conclusion, we postulate that suppressed dopaminergic inhibitory function on the hypophyseal-pituitary axis might be the mechanism for the increased PRL exhibited in the welders.