OBJECTIVE: To investigate risk factors for Creutzfeldt-Jakob disease (CJD) in patients in the United Kingdom treated with human pituitary growth hormone (hGH). METHODS: Incidence rates of CJD, based on person-year denominators, were assessed in a cohort of 1,848 patients treated with hGH in the United Kingdom from 1959 through 1985 and followed to the end of 2000. RESULTS: CJD developed in 38 patients. Risk of CJD was significantly increased by treatment with hGH prepared by the Wilhelmi method of extraction from human pituitaries. Risk was further raised if this treatment was administered at ages 8 to 10 years. The peak risk of CJD was estimated to occur 20 years after first exposure, and the estimated lifetime cumulative risk of CJD in Wilhelmi-treated patients was 4.5%. CONCLUSIONS: Size-exclusion chromatography, used in non-Wilhelmi preparation methods, may prevent CJD infection. Susceptibility to CJD may vary with age, and susceptibility may be present in only a few percent of the population.