Tropheryma whipplei, which causes Whipple disease, has been detected in 4% of fecal samples from the general adult population of France. To identify T. whipplei within families, we conducted serologic and molecular studies, including genotyping, on saliva, feces, and serum from 74 relatives of 13 patients with classic Whipple disease, 5 with localized chronic T. whipplei infection, and 3 carriers. Seroprevalence was determined by Western blot and compared with 300 persons from the general population. We detected T. whipplei in 24 (38%) of 64 fecal samples and 7 (10%) of 70 saliva samples from relatives but found no difference between persons related by genetics and marriage. The same circulating genotype occurred significantly more often in families than in other persons. Seroprevalence was higher among relatives (23 [77%] of 30) than in the general population (143 [48%] of 300). The high prevalence of T. whipplei within families suggests intrafamilial circulation.