Context: To prevent goiter and nodular hyperthyroidism, iodine fortification ( IF) of salt was introduced in Denmark in 1998. We prospectively registered all new cases of overt hyperthyroidism in two areas of Denmark before and for the first 6 yr after iodine fortification. Methods: We used a computer-based register of all new cases of hyperthyroidism in two population subcohorts with moderate iodine deficiency ( Aalborg, n = 310,124) and mild iodine deficiency ( Copenhagen, n = 225,707), respectively. Data were obtained 1) before IF ( 1997 - 1998); 2) during voluntary IF ( 1999 - 2000); 3) during the early ( 2001 - 2002) period of mandatory IF; and 4) during the late ( 2003 2004) period with mandatory IF. Results: The overall incidence rate of hyperthyroidism increased [ baseline, 102.8/100,000/year; voluntary IF, 122.8; early mandatory IF, 140.7; late mandatory IF, 138.7 ( P for trend <0.001)]. Hyperthyroidism increased in both sexes ( P <0.001) and in all age groups: 0-19, 20-39, 40-59, and 60+ yr ( P for trend <0.001). The increase was relatively highest in young adults aged 20-39 yr: late mandatory IF ( percent increase from baseline), age 20-39, 160%, P <0.001; age 40-59, 29%, P <0.01; age 60+ yr, 13%, P = not significant. Conclusion: Even a cautious iodization of salt results in an increase in the incidence rate of hyperthyroidism. Contrary to current concepts, many of the new cases were observed in young subjects, and are presumably of autoimmune origin. Furthermore, monitoring is expected to show a decrease in the number of elderly subjects suffering from nodular hyperthyroidism.