Recent outbreaks of diphtheria have drawn attention to the re-emergence of this disease. This study investigated susceptibility to diphtheria in north-east Germany and its relationship to gender and social factors. A study population of 4275 individuals recruited for the population-based Study of Health in Pomerania (SHIP) was available for analysis. IgG antibodies against diphtheria toxin were determined by ELISA and were used to define susceptibility to diphtheria (i.e., IgG titres < 0.1 IU/mL). The prevalence of susceptibility to diphtheria was 32.4%. Multivariate analysis revealed 45% increased odds of women being susceptible to diphtheria. Women who had not received diphtheria toxoid vaccination during the previous 10 years had four-fold increased odds of being susceptible to diphtheria toxin compared with unvaccinated men. None of the social factors investigated was associated with susceptibility status. It was concluded that a high proportion of middle-aged adults was susceptible to diphtheria. Women lacked seroprotection more often than men, which might be explained, in part, by gender-specific immune responses following vaccination. There is a need for information campaigns to improve public awareness of these problems.