Rectal swabs are generally considered less sensitive than fecal culture, but there are no data directly comparing human rectal swabs with fecal samples for detection of Salmonella. A phase I clinical study of a live oral attenuated Salmonella typhimurium vaccine strain in volunteers receiving a large known inoculum provided the opportunity to compare concurrent rectal swab and fecal cultures. Of 155 paired samples from 9 volunteers, 65 (42%) were culture positive: 35 (54%) by both methods, 20 (31%) by fecal culture only, and 10 (15%) by swab only. When compared with fecal culture, rectal swabs were 64% sensitive and 90% specific. Rectal swabs are of moderate diagnostic utility for detection of Salmonella and may be useful when collection of fecal samples is impractical.