In order to prove the association of opium addiction and cancer of the bladder, an extensive prospective case-control study with urine cytology in all registered opium addicts of Fars province in southern Iran was started in 1975. The urine cytology of the first 3,500 registered opium addicts revealed 15 cases of transitional cell carcinoma, and no cancer was detected among the 1,750 control cases. The crude incidence rate of bladder carcinoma in the general population over 20 years of age in Fars province is 6.6 per 100,000 males per year. The incidence rate among the opium addicts exceeded our expectations; thus, we decided to report the preliminary results of this study. The role of opium as a carcinogen in the bladder and the need for further investigation are discussed. The results of this study strongly suggest the use of routine urine cytology for opium addicts and long-term users of opiate alkaloid for the early detection of carcinoma of the bladder.