The large-scale resurgence of diphtheria in the former Soviet Union offered a unique opportunity to evaluate risk factors for the transmission of respiratory diphtheria; therefore, a prospective case-control study was done in the republic of Georgia. In total, 218 diphtheria cases (hospitalized between October 1995 and March 1996) and 408 matched controls participated. One hundred cases (45%) were </=14 years of age, and 118 (55%) were >/=15 years of age (range: <1 to 75 years). In the multivariate analyses, the following risk factors were found to be significant: lack of vaccination (matched odds ratio [mOR]=19.2), household exposure to diphtheria (mOR=7.4), exposure to skin lesions (mOR=5.8), history of eczema (mOR=3.4), fever with myalgia prior to illness (mOR=2.6), having tonsils (mOR=4.4), sharing a bed (mOR=1.9), sharing cups and glasses (mOR=2.7), and taking a bath less than once a week (mOR=2.6). These findings emphasize primary prevention through immunizations, secondary prevention following exposure to diphtheria (and to suspicious skin lesions), and adherence to strict standards of personal hygiene.