A study of serum testosterone and gonadotrophin concentrations in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (1746016) (TCDD) was conducted. The cohort consisted of 248 chemical production workers in New Jersey and Missouri who had been exposed to TCDD an average of 2.7 years between 1951 and 1969. The comparisons consisted of 231 persons not exposed to TCDD who lived near the chemical factories. The age range of the subjects was 31 to 81 years, mean 55 years. Blood samples were collected in 1987 and analyzed for serum TCDD, testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH). Because the serum TCDD concentrations were measured 15 to 37 years after exposure ended, the serum TCDD concentrations of each exposed worker at the time exposure ended were estimated. Associations between serum TCDD and FSH, LH, and testosterone concentrations were examined by logistic regression techniques. Serum TCDD concentrations in the exposed workers were divided into first, second, third, and fourth quartiles. Current serum TCDD concentrations corresponding to the quartiles were: below 20, 20 to 75, 76 to 240, and 241 to 3,400 picograms per gram (pg/g), respectively. The serum TCDD concentrations in the comparisons were below 20pg/g. The TCDD concentrations in the quartiles extrapolated back to the time exposure ended were below 140, 140 to 495, 496 to 1,860, and 1,860 to 30,000pg/g, respectively. Serum TCDD concentrations were positively associated with serum FSH and LH concentrations and inversely associated with testosterone concentrations after adjusting for smoking, alcohol consumption, age, diabetes, and body mass index. Significantly elevated serum LH concentrations were more prevalent in workers having serum TCDD concentrations in the second through fourth quartiles than in the comparisons. Significantly elevated serum FSH concentrations were more prevalent in workers in the fourth quartile. Significantly decreased serum testosterone concentrations were more prevalent in workers in the second through fourth quartile. The authors conclude that occupational exposure to TCDD alters the serum concentrations of male reproductive hormones.